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2A Medicine Sam > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

Give an overview of Thyroid hormone production, release and effects

A
  • Within the thyroid gland are numerous follicles each composed of an enclosed sphere of follicular cells surrounding a core containing a protein-rich material called the colloid.
  • Synthesis begins when circulating iodide is actively cotransported with Na+ ions across the basolateral membranes of the follicular cells - this is known as iodide trapping, the Na+ is pumped back out of the cells via Na+/K+- ATPases
  • The negatively charged iodide ions then diffuse to the apical membrane of the follicular cells and are transported into the colloid
  • The colloid of the follicles contains large amounts of a protein called thyroglobulin
  • Once inside the colloid iodide is rapidly oxidised to iodine which then bind to tyrosine residues on the thyroglobulin molecules (produced by the follicular cells) under the action of the enzyme thyroid peroxidase
  • The tyrosine may either bind to one iodine molecule - in which case its called a monoiodotyrosine (T1)
  • The tyrosine may bind to two iodine molecules - in which case its called a diiodotyrosine (T2)
  • When the thyroid is stimulated to produce thyroid hormone, the T1 and T2 molecules are cleaved from their tyrosine backbone (but are still attached to the thyroglobulin) and join to create T3 (T1 + T2) or T4 (T2 + T2)
  • For thyroid hormone to be secreted into the blood, extensions of the colloid-
    facing membranes of the follicular cells engulf portions of the colloid (with its iodinated thyroglobulin) by endocytosis
  • TSH (from pituitary) stimulates the movement of T3 & T4 containing colloid
    into secretory cells
  • The iodated thyroglobulin is then brought into contact with lysosomes in the cell interior
  • Proteolysis of the thyroglobulin results in the release of T3 & T4 which then are able to diffuse out of the follicular cells into the interstitial fluid and from there into the blood
  • There is sufficient iodinated thyroglobulin stored within follicles of the thyroid to provide thyroid hormone for several weeks even in the absence of dietary iodine - this is unique amongst endocrine glands
  • The thyroid produces more T4 than T3 - T3 is more active and is produced
    peripherally from the conversion of T4. More T4 is produced but T3 is more active.
  • The effects of T3/T4 are numerous:
    • BMR:increases the basal metabolic rate.
    • Metabolism:it hasanabolic effects at low serum levels andcatabolic effectsat higher levels.
    • Growth:increases release and effect of GH and IGF-1.
    • Cardiovascular:increases theheart rate and contractility through increasing sensitivity to catecholamines.
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2
Q

Give an overview of Thyroid disease (epidemiology, presentation, basic mechanism etc.)

A
  • Commonest endocrine disorder
  • More common in females than males
  • Hyperthyroidism has a 2.5% prevalence
  • Hypothyroidism has a 5% prevalence
  • Most common clinical presentation of thyroid disease is Goitre (5-15%):
    • A swelling of the thyroid gland that causes a palpable lump to form in the front of the neck
    • The lump will move up and down when you swallow
    • Mechanism is caused by TSH receptor stimulation which causes the thyroid to grow
    • Can be caused by BOTH hyperthyroidism and hypothyroidism
    • Hyperthyroidism: e.g. in graves’ there is excessive stimulation of the TSH receptor which stimulates the thyroid to produce more hormone and grow larger = goitre
    • Hypothyroidism: When pituitary detects low thyroid levels (due to iodine deficiency for example) it produces more TSH which in turn stimulates TSH receptors on the thyroid resulting in thyroid enlargement
    • Endemic in iodine deficient areas
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3
Q

Explain diffuse vs nodular or solitary thyroid presentations

A
  • Diffuse:
    • Physiological
    • Graves’ disease
    • Hashimoto’s thyroiditis
    • De Quervain’s
  • Nodular:
    • Multi-nodular
    • Adenoma/cyst
    • Carcinoma:
      • Papillary (70%), follicular (20%), anaplastic (<5%), lymphoma (2%) or medullary cell (5%)
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4
Q

Define Thyrotoxicosis

A
  • Excess of thyroid hormones in blood
  • 3 mechanisms for increased levels:
    • Overproduction of thyroid hormone - hyperthyroidism
    • Leakage of preformed hormone from thyroid: can be caused if follicular cells are destroyed by either infection or autoimmune thereby releasing 2-3 months supply of hormone
    • Ingestion of excess hormone
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5
Q

Define Hypothyroidism

A
  • Underproduction of thyroid hormone
  • Causes:
    • Primary hypothyroidism (reduced T4 and thus T3):
      • Primary atrophic hypothyroidism (PAH)
      • Hashimoto’s thyroiditis
      • Iodine deficiency
      • Post-thyroidectomy/radioiodine/anti-thyroid drugs
      • Lithium/amiodarone
    • Secondary hypothyroidism (reduced TSH from anterior pituitary):
      • Hypopituitarism
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6
Q

What are the actions of the adrenal hormones?

A
  • Aldosterone - works on kidney to increase blood volume, increase BP. May also cause hypernatraemia.
  • Cortisol - suppresses immune system, inhibits bone formation, increases metabolism - protein catabolism & lipolysis, gluconeogenesis, increases alertness.
  • Gonadocorticoids - production of oestrogen and testosterone. Main role is controlling libido.
  • Adrenaline and noradrenaline - gluconeogenesis, glycogenolysis, lipolysis, increase BP.
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7
Q

Define Hyperthyroidism

A

Hyperthyroidism is a common endocrine condition caused by an overactive thyroid gland causing an excess of thyroid hormone.

  • Hyperthyroidism:overactive thyroid gland (i.e. increasedthyroid hormone production) causing an excess of thyroid hormone and thyrotoxicosis.
  • Thyrotoxicosis:refers to an excess of thyroid hormone, having an overactive thyroid gland is not a prerequisite (e.g.consumption of thyroid hormone).
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8
Q

Epidemiology of Hyperthyroidism

A
  • The overall prevalence of hyperthyroidism is approximately 1.3% and increases to 4-5% in older women
  • Affects 2-5% of all women at some time
  • Mainly between 20-40yrs
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9
Q

Primary causes of Hyperthyroidism

A

Graves - Most common cause and underlying aetiology involves anti-TSH antibodies stimulating the thyroid gland - diffuse goitre and thyroid eye signs

Toxic multinodular goitre - Iodine deficiency leads to compensatory TSH secretion and hyperstimulation leading to nodular goitre formation. These nodules become TSH-independant and secrete thyroid hormones

Toxic adenoma - single autonomous functional nodule secreting thyroid hormone

Subclinical hyperthyroidism - Normal T3/T4 but low TSH. Can be caused by any of the above but is usually due to toxic multinodular goitre or Graves

Thyroiditis - In the initial stages of thyroiditis, including Hashimotos and De Quervains thyroiditis, there can be transient hyperthyroid state which is then followed by hypothyroid state

Drugs - Amiodarone

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10
Q

Secondary causes of Hyperthyroidism

A

Pituitary adenoma - TSH-secreting pituitary adenoma

Ectopic tumour - such as hCG-secreting tumours e.g. choriocarcinoma

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10
Q

Secondary causes of Hyperthyroidism

A

Pituitary adenoma - TSH-secreting pituitary adenoma

Ectopic tumour - such as hCG-secreting tumours e.g. choriocarcinoma

Hypothalamic tumour - Excessive TRH secretion - v rare

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11
Q

Other causes of Hyperthyroidism

A
  • Beta-HCG related - Beta-HCG is thought to mimic the action of TSH causing thyroid hormone synthesis and release. It occurs in states of elevated Beta-HCG e.g. pregnancy, choriocarcinoma.
  • Ectopic thyroid tissue - thyroid tissue found elsewhere that produces thyroid hormone.
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12
Q

Risk factors for Hyperthyroidism

A
  • Family history
  • Auto-immune disease e.g. vitiligo, type 1 diabetes, Addison’s disease
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13
Q

Pathophysiology of Hyperthyroidism (Pri and Sec)

A

Hyperthyroidism describes increased levels of circulating thyroid hormone leading to raised metabolic rate and sympathetic nervous system activation.

Primary hyperthyroidisminvolves an excessive production of T3/T4 by the thyroid gland due to pathology affecting the thyroid gland itself.

Secondary hyperthyroidismoccurs due to excessive stimulation of the thyroid gland by TSH, secondary to pituitary or hypothalamic pathology, or from an ectopic source such as a TSH-secreting tumour.

Primary hyperthyroidism is the most common subtype, whilst secondary hyperthyroidism is rare.

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14
Q

Key presentations of Hyperthyroidism

A

Mnemonic - Thyroidism: tremor, heart rate increase, yawning, restless, oligomenorrhoea, irritability, diarrhoea, intolerance to heat, sweating, muscle wasting (weight loss).

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15
Q

Signs of Hyperthyrodism

A
  • Postural Tremor
  • Palmar erythema
  • Hyperreflexia
  • Sinus tachycardia/ arrhythmia
  • Goitre
  • Lid lag and retraction
  • Specific to Graves’ disease:
    • Thyroid acropachy (thickening of the extremities)
    • Thyroid bruit
    • Pretibial myxoedema (localised lesions of the skin)
    • Eye signs
      • Exophthalmos (bulging of the eye)
      • Ophthalmoplegia (paralysis or weakness of the eye muscles)
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16
Q

Symptoms of Hyperthyroidism

A
  • Weight loss
  • Anxiety
  • Fatigue
  • Reduced libido
  • Heat intolerance
  • Palpitations
  • Menstrual irregularity
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17
Q

First line investigations for Hyperthyroidism

A

Thyroid function tests:
- Primary or Graves: Low TSH, High T4
- Subclinical hyperthyroidism: Low TSH, normal T4
- Secondary: High or normal TSH and high T4

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18
Q

Other investigations for Hyperthyroidism

A
  • Antibodies: anti-TSH receptorantibodies are positive in 95% of patients with Graves’. Anti-TPO (thyroid peroxidase) and anti-thyroglobulin antibodies may also be positive
  • If there is serological confirmation, there is no need for imaging
  • Thyroid ultrasound:offered to patients with thyrotoxicosisif they have a palpable thyroid noduleorin patients with normal thyroid function when malignancy is suspected
  • Technetium radionuclide scan:usually performed if anti-TSH antibodies are negative. ShowsdiffuseuptakeinGraves’ disease, unlike in toxic adenoma or toxic multinodular goitre
  • Glucose:hyperthyroidism is associated with hyperglycaemia
  • ECG: hyperthyroidism is associated with atrial fibrillation
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19
Q

Differential diagnosis for hyperthyroidism

A
  • Usually is clinically obvious
  • Differentiation of mild cases from anxiety can be difficult, look for:
    • Eye signs e.g. lid lag & stare
    • Diffuse goitre
    • Proximal myopathy & wasting
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20
Q

1st line management for hyperthyroidism

A
  • Beta blocker e.g. propranolol for symptomatic relief
  • Anti-thyroid medication: preferred in mild disease
    • Short-term: to restore euthyroidism prior to definitive treatment (radioiodine or surgery)
    • Medium-term: to induce remission; 12-18 months for mild disease
    • Long-term: if radioiodine or surgery is declined or contraindicated
    • 1st line anti-thyroid medication is Carbimazole
      • Titration:start carbimazole at 40mg andreducethe dose gradually until euthyroid
      • Block and replace:start carbimazole at 40mg and add thyroxine when euthyroid
  • Radioiodine treatment: first line treatment in more than mild Graves’ or toxic multinodular goitre
    • Contraindicated inpregnancy, age < 16 years old, when breastfeeding or those with established eye disease as can make eye symptoms worse
    • Advice for patients post-treatment:
      • Avoid close contact with pregnant women and children for3 weeks
      • Avoid becoming pregnant for6 months
      • Must avoid fathering children for4 months
    • Patients often require long-termlevothyroxineafter radioiodine therapy
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21
Q

Adjunctive therapy for hyperthyroidism

A
  • Second line antithyroid medication if Carbimazole not used = Propylthiouracil, but this is associated with hepatotoxicity. In pregnancy, propylthiouracil is used in the first trimester and this is switched to carbimazole thereafter as per NICE
  • Surgery:total or hemithyroidectomy
    • Optimisation with antithyroid drugs is vital, aiming forpre-operative euthyroidism
    • Indicated in those at high risk of recurrent hyperthyroidism or when other options fail
    • Hemithryoidectomy is preferred for a single thyroid nodule
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22
Q

Complications of hyperthyroidism management

A
  • Surgery complications - risk of hypothyroidism, hypoparathyroidism, and recurrent laryngeal nerve palsy resulting in a hoarse voice, trachael compression from post-operative bleeding
  • Anti-thyroid drugs - agranulocytosis and neutropenia or hepatotoxicity
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23
Q

Complications of hyperthyroidism

A
  • Cardiovascular: heart failure, atrial fibrillation
  • Musculoskeletal:osteoporosis, proximal myopathy
  • Thyrotoxic crisis/ thyroid storm - rapid T4 increase. Medical emergency!
    • Features include hyperpyrexia, tachycardia, extreme restlessness
      and eventually delirium, coma and death
    • Treated with large doses of carbimazole, propranolol, potassium iodide, IV hydrocortisone to stop conversion of T4 to T3
  • Iatrogenic (due to treatment):
    • Agranulocytosis and neutropaenic sepsis: secondary to carbimazole
    • Hepatotoxicity: secondary to propylthiouracil
    • Congenital malformations: carbimazole in first trimester
    • Foetal goitre and hypothyroidism: any antithyroid medication in pregnancy at high doses
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24
Q

Prognosis for hyperthyroidism

A

Prognosis depends on the underlying cause and severity. Patients may well become hypothyroid during the course of their management and require levothyroxine to achieve a euthyroid status.

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25
Q

Define Graves disease

A

Graves’ disease is the most common cause of hyperthyroidism worldwide. It is an autoimmune induced excess production of thyroid hormone

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26
Q

Epidemiology of Graves

A
  • This is the MOST COMMON CAUSE of hyperthyroidism (2/3rds of cases)
  • More common in FEMALES than males
  • Typically presents at 40-60yrs (appears earlier if maternal family history)
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27
Q

Aetiology of Graves

A
  • Serum IgG antibodies, specific for Graves’ disease, known as TSH receptor stimulating antibodies (TSHR-Ab) bind to TSH receptors in the thyroid
  • Thereby stimulating thyroid hormone production (T3 & T4) - essentially they behave like TSH
  • Resulting in excess secretion of thyroid hormones and hyperplasia of thyroid follicular cells resulting in hyperthyroidism and diffuse goitre
  • Persistent high levels predict a relapse when drug treatment is stopped
  • Similar auto antigen can also result in retro-orbital inflammation - graves opthalmopathy
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28
Q

Risk Factors for Graves

A
  • Family history
  • Female
  • Autoimmune disease
  • Stress
  • High iodine intake
  • Radiation
  • Tobacco use
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29
Q

Pathophysiology of Graves

A

Involves anti-TSH antibodies causing increased thyroid hormone production through stimulation of the TSH receptor. Of note, anti-TSH antibodies react with orbital antigens in fat and connective tissue, causing retro-orbital inflammation which leads to thyroid eye disease.

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30
Q

Signs and symptoms of Graves

A
  • Thyroid acropachy - clubbing, swollen fingers and periosteal bone formation
  • Thyroid bruit - continuous sound heard over thyroid mass
  • Pretibial myxoedema - raised, purple-red symmetrical skin lesions over the anterolateral aspects of the shin
  • Eye signs
    • Exophthalmos - protruding eye
    • Ophthalmoplegia - paralysis or weakness of eye muscles
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31
Q

First line investigations for Graves

A

TFT’s: raised T3 and T4, reduced TSH.

All other aspects of investigation and management are the same as generic hyperthyroidism

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32
Q

Explain toxic multinodular goitre

A
  • Nodules that secrete thyroid hormones
  • Seen in elderly and in iodine-deficient areas
  • Commonly occurs in older women and drug therapy rarely produces prolonged remission
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33
Q

Explain solitary toxic adenoma

A
  • Cause of about 5% of cases of hyperthyroidism
  • Prolonged remission is rarely induced by drug therapy
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34
Q

Explain De Quervains thyroiditis

A
  • Transient hyperthyroidism sometimes results from acute inflammation of the thyroid gland, probably due to viral infection
  • Typical for there to be globally reduced uptake on technetium thyroid scan
  • Usually accompanied by fever, malaise and pain in the neck
  • Treat with aspirin and only give prednisolone for severely symptomatic cases
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35
Q

Explain drug induced hyperthyroidism

A
  • Amiodarone - anti-arrhythmic drug: Can cause both hyperthyroidism (due to the high iodine content of amiodarone) and hypothyroidism (since it also inhibits the
    conversion of T4 to T3)
  • Iodine
  • Lithium
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36
Q

Define Thyrotoxic Crisis

A

Also known as a ‘thyroid storm’, a thyrotoxic crisis is a life-threatening complication of hyperthyroidism and is most commonly seen in patients with Graves’ disease or toxic multinodular goitre.

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37
Q

Aetiology of Thyrotoxic Crisis

A

It is classified as an endocrine emergency and it often occurs secondary to a precipitating factor such as infection or trauma in patients with known hyperthyroidism. However, it may also be the first manifestation of undiagnosed hyperthyroidism.

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38
Q

Signs of Thyrotoxic Crisis

A
  • Hyperpyrexia: often > 40°C
  • Tachycardia: often > 140 BPM, with or without atrial fibrillation
  • Reduced GCS - consciousness
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39
Q

Symptoms of Thyrotoxic Crisis

A
  • Nausea and vomiting
  • Diarrhoea
  • Abdominal pain
  • Jaundice
  • Confusion, delirium or coma
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40
Q

Investigations for Thyrotoxic Crisis

A
  • TFTs: elevated T3 and T4 levels, suppressed TSH levels
  • ECG: tachycardia; may demonstrate atrial fibrillation
  • Blood glucose: perform in all patients with reduced consciousness
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41
Q

Management for Thyrotoxic Crisis

A
  • Conservative: IV fluids, NG tube insertion (if vomiting), tepid sponging, paracetamol, ITU admission
  • Antithyroid drugs: propylthiouracil is generally preferred, but carbimazole is an alternative
  • Corticosteroid: IV hydrocortisone or methylprednisolone
  • Beta-blocker: propranolol PO, or IV over 10 minutes
  • Oral iodine: Lugol’s iodine is offered > 1 hour after propylthiouracil (some trusts advise giving it at 4 hours) - blocks the peripheral conversion of T4 to T3
  • Sedation: if required, use chlorpromazine
  • Plasma exchange or thyroidectomy: in refractory patients
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42
Q

Prognosis of Thyrotoxic Crisis

A

Even if promptly treated, it has a mortality of 10-20%

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43
Q

Define Hypothyroidism

A

Hypothyroidism is a common endocrine condition caused by a deficiency in thyroid hormone.

Hypothyroidism is a pathological state reflecting a reduction in circulating T3 and T4. Hypothyroidism is classified as primary, secondary and congenital. 95% of cases are primary, with secondary and congenital causes being rare.

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44
Q

Epidemiology of Hypothyroidism

A
  • It is estimated that the prevalence of any cause of hypothyroidism is 1-2%, with Hashimoto’s thyroiditis being the most common cause in the developed world. Iodine deficiency is the most common cause worldwide.
  • Female gender: 5-8x more likely to develop than men
  • Middle-aged: peak age is 30-50 years old in Hashimoto’s thyroiditis
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45
Q

Aetiology of Hashimoto’s thyroiditis and specific epidemiology and symptoms

A

Hashimoto’s thyroiditis:commonest cause in the developed world

  • Autoimmune process associated withHLA-DR5andanti-TPO antibodies,which act as competitive inhibitors for the enzyme
  • Associated with other autoimmune conditions e.g. type 1 diabetes and Addisons disease
  • Diffuse painless goitre and can experience a transient thyrotoxic state known ashashitoxicosis
  • 5-10x more common in women
  • Increased risk of Non-Hodgkin lymphoma
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46
Q

Aetiology of De Quervains thyroiditis

A
  • Follows a viral prodrome and can also present with a transientthyrotoxicstate
  • Painfulgoitre withraised inflammatory markers. Usually self-limiting
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47
Q

Aetiology of post partum thyroiditis

A
  • Autoimmune with most patients developingthyrotoxicosiswithin the first 6 months of birth, with subsequenthypothyroidism
  • Most patients’ thyroid function normalises by 12 months
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48
Q

Aetiology of Riedels thyroiditis

A
  • Hard non-tender thyroid goitre due to fibrous tissue
  • Causes a painless goitre
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49
Q

Aetiology of Iodine deficiency

A
  • Commonest causeworldwide, due to dietary deficiency
  • Uncommon in the developed world due to iodine-fortified salt and foods
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50
Q

Aetiology of Post-thyroidectomy or post-radioiodine

A

After treatment for hyperthyroidism e.g. Graves’ disease, patients can experience long term hypothyroidism and require levothyroxine replacement

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51
Q

Drug causes of Hypothyroidism

A
  • Amiodarone - can cause both hyperthyroidism (due to the high iodine content of amiodarone) and hypothyroidism (since it also inhibits the conversion of T4 to T3)
  • Lithium
  • Anti-thyroid drugs e.g. carbimazole
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52
Q

Secondary causes of Hypothyroidism

A
  • Often due to compression from apituitary tumour(e.g. adenoma), but may occur following surgery/radiation or vascular pathology (e.g. pituitary apoplexy)
  • Rarely, it may be due tohypothalamicpathology, e.g. a tumour
  • Drugs: cocaine, steroids and dopamine all inhibit TSH secretion
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53
Q

Risk factors for hypothyroidism

A
  • Family history
  • History of autoimmunity
  • Genetic disorders: Turner and Down syndrome
  • Chest or neck irradiation
  • Thyroidectomy or radioiodine
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54
Q

Pathophysiology of hypothyroidism

A

Hypothyroidism is a pathological state reflecting a reduction in circulating T3 and T4. 95% of cases are primary, with secondary causes being rare.

Primary hypothyroidismis due to pathology affecting the thyroid gland itself, such as an autoimmune disorder (e.g. Hashimoto’s thyroiditis) or iodine deficiency.

Secondary hypothyroidismis usually due to pathology affecting thepituitarygland (e.g. pituitary apoplexy) or a tumour compressing the pituitary gland. It may also be caused byhypothalamicdisorders and certain drugs.

Congenital hypothyroidismoccurs due to an absent or poorly developed thyroid gland (dysgenesis), or one that has properly developed but cannot produce thyroid hormone (dyshormonogenesis).

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55
Q

Signs of Hypothyroidism

A
  • Dermatological: hair loss, loss of lateral aspect of the eyebrows (Queen Anne’s sign), dry and cold skin, coarse hair
  • Bradycardia
  • Goitre
  • Decreased deep tendon reflexes
  • Carpal tunnel syndrome
  • Hoarse voice
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56
Q

Symptoms of hypothyroidism

A
  • Myxoedema - seen in autoimmune hypothyroidism
  • Fluid retention - oedema, pleural effusions, ascites
  • Weight gain
  • Cold intolerance
  • Lethargy
  • Dry skin
  • Constipation
  • Menorrhagia: followed later by oligomenorrhoea and amenorrhoea
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57
Q

First line investigations for hypothyroidism

A

Thyroid function tests (TFTs) - decreased T3/T4 and increased TSH in primary disease.

Increased TSH and normal T4 in subclinical

Decreased or normal TSH and decreased T4 signals Secondary hypothyroidism

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58
Q

Following investigations in hypothyroidism

A

Antibodies: Anti-TPO is associated with Hashimoto’s thyroiditis in 95% of cases, also look for Anti-TPO, Anti-thyroglobulin

Inflammatory markers: raised in De Quervains thyroiditis

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59
Q

Other investigations for hypothyroidism

A
  • Ultrasound:not routinely carried out but may be useful if there is a goitre or focal nodule and malignancy is suspected in patients with normal thyroid function
  • Radionuclide scan:not routinely carried out. Uses a small dose of a radioactive chemical (isotope) called a tracer that can detect cancer, trauma, infection or other disorders.
  • Fasting lipids:hypothyroidism is associated with hypercholesterolemia
  • Serum glucose and HbA1c:hypothyroidism is associated with hypoglycaemia. Also, Hashimoto’s thyroiditis is associated with T1DM
  • FBC and serum B12 level: autoimmune thyroid disease is associated with a higher risk of pernicious anaemia
  • Coeliac serology: to assess for coeliac disease if autoimmune thyroid disease is suspected. Thyroid disease is more common in patients with coeliac disease.
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60
Q

Aims of treatment for hypothyroidism

A

The aims of treatment are to resolve signs and symptoms and to maintain serum TSH and FT4 levels within or close to the normal reference range (0.5-2.5 mU/L). All patients with secondary hypothyroidism require urgent referral to an endocrinologist.

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61
Q

1st line management for hypothyroidism

A
  • Levothyroxine (T4):offer with regular review of symptoms and TSH every 3 months. Once TSH is stable (on 2 occasions at least 6 months apart), review TSH annually
    • T4 starting dose: 50-100 mcg OD for most patients
    • Lower T4 starting dose: 25 mcg OD titrated slowly if > 50 years, severe hypothyroidism or a history of ischaemic heart disease
  • Advise that symptoms may lag behind treatment changes for several weeks or months
  • Review dose every8-12 weekswhen dose is changed
  • Interactions: iron and calcium carbonatereducelevothyroxine absorption so should be given ≥ 4 hours apart
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62
Q

Pregnancy/postpartum management for hypothyroidsm

A
  • If TFTs are abnormal, advise delaying conception and using contraception until stabilised on levothyroxine
  • Inform the woman that there is anincreased demand for levothyroxinein pregnancy, with the dose usually increased by at least 25-50 mcg and aiming for a low-normal TSH
  • Post-partum thyroiditis: the hypothyroid state may require levothyroxine, with most patients’ thyroid function normalising by 12 months of the birth
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63
Q

Complications of hypothyroidism

A
  • Cardiovascular:hypercholesterolaemia is associated with ischaemic heart disease
  • Neurological:carpal tunnel syndrome, peripheral neuropathy, proximal myopathy
  • Myxoedema coma:rare but potentially fatal outcome of untreated/undertreated hypothyroidism. Presents with confusion, hypothermia, hypoglycaemia, hypoventilation, and hypotension
  • Thyroid lymphoma:patients with Hashimoto’s thyroiditisare at increased risk of lymphoma, usually diffuse large B cell lymphomas
  • Thyroxine side-effects
    • Hyperthyroidism
    • Atrial fibrillation
    • Osteoporosis
    • Angina
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64
Q

Prognosis for Hypothyroidism

A

Hypothyroidism, if well managed with levothyroxine, will not present any issues for the individual and euthyroid status can be achieved. However, if left untreated, hypothyroidism slowly develops and worsens and predisposes to the above complications.

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65
Q

Define Hashimotos thyroiditis

A

The most common cause of hypothyroidism in the West. Antithyroid antibodies is the cause for this type of hypothyroidism

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66
Q

Epidemiology of Hashimotos thyroiditis

A
  • It is estimated to affect between 0.5% and 2% of the population.
  • More common in FEMALES than males
  • Incidence increases with age
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67
Q

Risk factors for Hashimotos thyroiditis

A
  • Female sex
  • Associated with other autoimmune disease e.g. T1DM
  • Associations with Turner’s and Down’s syndrome
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68
Q

Pathophysiology of Hashimotos thyroiditis

A

Autoimmune inflammation of thyroid gland. This is associated with anti thyroid peroxidase (TP) antibodies and anti-thyroglobulin antibodies. There may also be anti-TSH receptor antibodies leading to degeneration of thyroid gland.

(Thyroid peroxidase converts iodide into iodine and is essential for thyroid hormone production. As is thyroglobulin)

It exists in two forms:

  • Goitrous:characterised by a firm and rubbery goitre
  • Atrophic:characterised by an atrophic gland

Initially it causes goitre, after which there is atrophy of the thyroid gland

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69
Q

Define thyroid cancer

A

Cancers of the thyroid gland: Four types account for more than 98% of thyroid malignancies: papillary, follicular, anaplastic, and medullary.

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70
Q

Epidemiology of Thyroid cancer

A
  • Thyroid cancer is the most common endocrinological malignancy
  • Not generally common, but are responsible for 400 deaths annually in the UK
  • More common in women than men, generally
  • Most likely to be diagnosed between the ages of 45 to 54 years.
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71
Q

Clinical manifestations of thyroid cancers

A
  • Palpable thyroid nodule in most cases
  • Occasionally (5%) they present with cervical lymphadenopathy or with lung,
    cerebral, hepatic or bone metastases
  • Thyroid gland may increase in size, become hard and may be irregular in shape
  • Tracheal deviation
  • Neck enlargement
  • Dysphagia
  • Hoarseness of voice
  • Dyspnoea
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72
Q

1st line investigations for thyroid cancer

A
  • Fine needle biopsy - To distinguish between benign or malignant nodules
  • TFTs - To check if hyperthyroid or hypothyroid (TSH, T3 & T4) - needs to be treated before carcinoma surgery
  • Ultrasound of neck - Can differentiate between benign or malignant
  • Laryngoscopy - paralysed vocal cord is highly suggestive of malignancy
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73
Q

Epidemiology of papillary thyroid tumours

A
  • Most frequent (around 80%)
  • F>M
  • Peak incidence 30s-50s
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74
Q

Pathophysiology of papillary thyroid cancer

A
  • These cancers are derived from the follicular cells - they secrete thyroglobulin and take up radioiodine
  • They can spread via lymphatic invasion to cervical nodes and neck
  • They are slow growing
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75
Q

Risk factors for papillary thyroid cancers

A
  • Radiation exposure
  • Mutation RET and BRAF
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76
Q

Management for thyroid papillary cancer

A
  • Lobectomy (or total thyroidectomy with lymph node removal)
  • High risk patients may receive radioiodine to catch the cancer that may not have been resected
  • TSH suppression with thyroid hormone replacement (TSH is a growth factor for the cancer)
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77
Q

Prognosis for papillary thyroid cancer

A

Associated with best prognosis (10 year survival >95%)

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78
Q

Epidemiology of Follicular thyroid cancer

A
  • 10% of thyroid cancers
  • F>M
  • Peak in 40s-60s
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79
Q

Pathophysiology of follicular thyroid cancer

A
  • Derived from follicular cells - secretes thyroglobulin and takes up radioiodine
  • Hurthle cells (a subtype of follicular cells) seen
  • Early metastases
  • Can spread via vascular invasion: locally invasive, invades thyroid capsule
  • Distal spread more common than papillary
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80
Q

Risk factors for follicular thyroid cancer

A

Mutations in RAS

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81
Q

Management for follicular thyroid cancer

A
  • Lobectomy (or total thyroidectomy with lymph node removal)
  • High risk patients may receive radioiodine to catch the cancer that may not have been resected
  • TSH suppression with thyroid hormone replacement
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82
Q

Prognosis for follicular thyroid cancer

A
  • More aggressive than papillary
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83
Q

Epidemiology of Medullary thyroid cancer

A
  • 5% of thyroid cancers
  • Sporadic (80%) - F>M, peak in 40s-60s
  • Familial (20%) - F:M, peak onset at early age
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84
Q

Pathophysiology of medullary thyroid cancer

A
  • Derived from para-follicular cells (aka C-Cells responsible for calcitonin production) - do not secrete thyroglobulin and does not take up radioiodine
  • Associated with early metastasis
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85
Q

Risk factors for Medullary thyroid cancer

A
  • Family with MEN 2A and 2B
  • Mutation in RET
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86
Q

Management for medullary thyroid cancer

A
  • Lobectomy (maybe total thyroidectomy with lymph node removal)
  • Thyroid hormone replacement for normal TSH (no TSH suppression)
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87
Q

Prognosis for medullary thyroid cancer

A

More aggressive than follicular

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88
Q

Epidemiology of Anaplastic thyroid cancer

A
  • 3% of thyroid cancers
  • M>F
  • Peak in 60s to 80s
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89
Q

Pathophysiology of Anaplastic thyroid cancers

A
  • Also known as undifferentiated carcinoma due to poor differentiation
  • Very aggressive
  • Spread: infiltrative to local structures, soft tissue of neck, widespread metastases, early mortality
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90
Q

Management for anaplastic thyroid cancer

A
  • Does not respond to radioactive iodine
  • If possible a total thyroidectomy is done
  • Combined chemotherapy and radiation - may be palliative
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91
Q

Prognosis for anaplastic thyroid cancer

A

Worst prognosis

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92
Q

Explain Lymhoma for thyroid including management

A
  • Generally a B cell-type non-Hodgkin’s lymphoma. It generally arises in the setting of pre-existing Hashimoto’s thyroiditis.
  • Management
    • Primary thyroid lymphoma is treated with a combination of radiation and chemotherapy. The most common chemotherapy regimen is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone).
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93
Q

Differential diagnosis for thyroid cancer

A
  • Goitre
  • Benign thyroid nodule
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94
Q

Complications of thyroid cancer

A
  • Airway obstruction
  • Surgery related:
    • Hypoparathyroidism
    • Recurrent laryngeal nerve damage
    • Bleeding
  • TSH suppression related:
    • Atrial fibrillation
    • Bone mineral loss
  • Radioiodine related:
    • Secondary tumours
    • Dryness of mouth
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95
Q

Define Cushings syndrome

A

Cushing syndrome is the clinical manifestation of pathological hypercortisolism from any cause.

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96
Q

Epidemiology of Cushings

A
  • Cushing’s syndrome is uncommon, with an estimated 1-10 cases per million in the population
  • It most commonly affects people aged 20 to 50 years
  • Occurs 3 times more commonly in women than in men
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97
Q

Aetiology of Cushings

A
  • Iatrogenic - due to exogenous steroid use
  • Cushing’s disease - a pituitary adenoma secreting excess ACTH
  • Primary disease - e.g. adrenal adenoma or adrenal hyperplasia - secreting excess cortisol
  • Paraneoplastic Cushing’s- cancer producing ectopic ACTH e.g. from small cell lung cancer or neuroendocrine tumours
  • Carney complex - a genetic disorder with multiple benign tumours, e.g. cardiac myxoma
  • Micronodular adrenal dysplasia - rare cause
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98
Q

Risk factors for Cushings

A
  • Long term steroid use
  • Pituitary adenoma
  • Adrenal adenoma
  • Small cell lung cancer
  • Neuroendocrine tumours
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99
Q

Signs of Cushings

A
  • Hypertension
  • Moon face
  • Buffalo hump
  • Central adiposity
  • Violaceous striae
  • Muscle wasting and proximal myopathy
  • Ecchymoses and fragile skin
  • Acne
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100
Q

Symptoms of Cushings

A
  • Bloating and weight gain
  • Mood change
  • Tiredness
  • Easy bruising
  • Increase susceptibility
  • Menstrual irregularity
  • Reduced libido
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101
Q

1st line investigations for Cushings

A

Afterexcluding exogenous glucocorticoid use, the first step is toconfirm hypercortisolismwhich can be done with any of the following:

  • 24-hour urinary free cortisol
  • Overnight dexamethasone suppression test:most sensitive; shows failure of cortisol suppression
  • Low dose dexamethasone suppression test:shows failure of cortisol suppression
  • Late-night salivary cortisol - helps to demonstrate a loss of the normal circadian pattern.
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102
Q

Gold standard investigations for Cushings

A
  • 24-hour urinary free cortisol
  • Overnight dexamethasone suppression test
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103
Q

Tests to determine causes of Cushings

A

Once hypercortisolism is confirmed, the source must belocalised:

  • 9am ACTH:
    • Ifelevated: suggests anACTH-dependentcause and warrants ahigh dose dexamethasone suppression test
    • Iflow: suggests anACTH-independentcause and warrants aCT adrenalsto look for adrenal pathology
  • High dose dexamethasone suppression test (DST):suppression of cortisol occurs in Cushing’s disease (pituitary adenoma), butnotin an ectopic ACTH source
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104
Q

Other tests to consider for Cushings

A

If a DST isinconclusive:

  • CRH stimulation test:
    • Pituitary source: cortisol rises
    • Ectopic or adrenal source: no change in cortisol
  • Petrosal sinus sampling of ACTH: to differentiate between pituitary and ectopic ACTH source

Final localisation tests:

  • MRI pituitary:if Cushing’s disease (pituitary adenoma)is suspected
  • CT chest, abdomen and pelvis: if an ectopic source is suspected
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105
Q

Differential diagnosis for Cushings

A
  • Obesity
  • Metabolic syndrome
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106
Q

Management for Cushings

A

ACTH-dependent causes:

  • Cushing’s disease (pituitary adenoma):first-line treatment is withtrans-sphenoidal resectionof the pituitary. There is a role for medical therapy (e.g. glucocorticoid antagonists) or radiotherapy if surgery fails
  • Ectopic ACTH source:treatment of underlying cancer

ACTH-independent causes:

  • Iatrogenic:review the need for medication and try weaning if possible
  • Adrenal tumour:tumour resection or adrenalectomy
    • Unilateral adrenal adenomaUnilateral adrenalectomy offers curative therapy. Where available the laparoscopic approach is generally preferred to open surgery. Following surgery patients will need a tapering course of exogenous steroids for a period of time as their endogenous CRH and ACTH will be suppressed.
    • Bilateral adrenal hyperplasiaIn patients with overt Cushing’s bilateral adrenalectomy may be offered. Following this patients require replacement of glucocorticoids and mineralocorticoids.
    • Adrenal carcinomaFollowing appropriate staging resection is the mainstay of management. Adjuvant chemotherapy, radiotherapy or mitotane may be given.
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107
Q

Monitoring for Cushings

A

Recurrence of adrenocorticotrophic hormone-dependent Cushing syndrome is common, with at least a 5% to 26% risk of recurrence at 5 years. Patients who have achieved remission should be screened periodically (every 6-12 months) for recurrence of disease.

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108
Q

Complications of Cushings

A

Complications associated with action of cortisol -

  • Osteoporosis
  • Increased susceptibility to infection
  • Diabetes mellitus
  • Hypertension

Treatment related -

  • Hypopituitarism
  • Adrenal insufficiency
  • Nelson syndrome after bilateral adrenalectomy - enlarged pituitary, development of adenomas.
  • Hypothyroidism
  • Growth hormone deficiency
  • Hypogonadism
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109
Q

Prognosis for Cushings

A

The prognosis depends on the underlying cause. Adrenal adenomas and pituitary microadenomas are associated with a favourable outcome. Those with adrenal carcinomas have poor outcomes. The prognosis in ectopic ACTH production depends on the underlying malignancy, but many are aggressive and grow rapidly.

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110
Q

Explain pseudo-Cushings

A
  • Cushingoid features and abnormal cortisol levels butnotassociated with HPA pathology
  • Common causes include alcohol excess, severe depression, obesity, pregnancy
  • Results in afalse positivedexamethasone suppression test and 24h urinary free cortisol
  • Differentiated using an insulin stress test
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111
Q

Explain overnight dexamethasone suppression test

A

Dexamethasone should, in the healthy patient, send negative feedback to the pituitary and hypothalamus resulting in ↓ ACTH and thus reduced cortisol.

  • Oral dexamethasone 1mg at 00:00
  • Measure serum cortisol at 8AM
  • Normally there will be cortisol suppression < 50nmol/L
  • In Cushing’s syndrome there will be no suppression
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112
Q

Explain GH secretion and control

A

Growth hormone (GH) is secreted in a pulsatile fashion under the control of two hypothalamic hormones:

  • Growth hormone releasing hormone (GHRH) stimulates GH secretion
  • Somatostatin (SST) inhibits GH secretion

GH is also inhibited by high glucose and dopamine

Ghrelin (synthesised in the stomach) also stimulates release of GH

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113
Q

How does GH exert its actions

A
  • Indirectly through the induction of insulin-like growth factor (IGF-1), which is
    synthesised in the liver and other tissues
  • Directly on tissues such as the liver, muscle, bone or fat to induce metabolic
    changes
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114
Q

Define Acromegaly

A

Acromegaly is a condition caused by an excess of growth hormone (GH) most commonly related to a pituitary adenoma.

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115
Q

Define Gigantism

A

Gigantism refers to excess GH production before fusion of the epiphyses of the long bones

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116
Q

Epidemiology of Acromegaly

A
  • Acromegaly is a rare disease with a prevalence of < 0.1%
  • Acromegaly is often recognised in middle-aged men or women but can occur at any age.
  • The disease is equally distributed between both sexes.
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117
Q

Aetiology of Acromegaly

A
  • Pituitary adenomas account for > 90% of cases of acromegaly.
  • Other causes of acromegaly are very rare. They are related to excess secretion of GHRH or GH:
    • Ectopic release of GH: May be seen in neuroendocrine tumours.
    • Ectopic release of GHRH: Related to tumours including carcinoid and small cell lung cancer.
    • Excess hypothalamic release of GHRH: Related to hypothalamic tumours.
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118
Q

Risk Factors for Acromegaly

A
  • MEN-1:pituitary adenomas, primary hyperparathyroidism, and pancreatic neuroendocrine tumours; MEN-1 is present in 6% of cases
  • McCune-Albright syndrome
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119
Q

Pathophysiology of Acromegaly

A

Acromegaly describes a state of excessive growth hormone (GH) production.A pituitary somatotroph adenomais responsible in over 95% of cases, but acromegaly can rarely occur due to ectopic secretion from a GHRH or GH producing-tumour, such as a pancreatic tumour.

Excessive GH causessoft-tissue growth resultingin the classical appearance seen in the disease. Additionally, if sufficiently large, a pituitary adenoma can causebitemporal hemianopia, and significant compression can lead to panhypopituitarism.

120
Q

Signs of Acromegaly

A
  • Bitemporal hemianopia: due to compression of optic chiasm by pituitary tumour
  • Facial features:
    • Prominent jaw and supra-orbital ridge
    • Coarse facial appearance
    • Prognathism: protrusion of the lower jaw
    • Splaying of teeth
    • Macroglossia: large tongue
  • Spade like hands
  • Sweaty palms and oily skin
  • Hypertension
  • Organomegaly
121
Q

Symptoms of Acromegaly

A
  • Visual disturbance
  • Headaches
  • Obstructive sleep apnoea
  • Rings and shoes are tight
  • Polyuria and polydispia due to T2DM
  • Tingling in hands: carpal tunnel sydrome
  • Hyperprolactinaemia: raised prolactin seen in over 20% of cases - features include galactorrhea, dysmenorrhoea, hypogonadism, decreased libido and infertility.
122
Q

1st line investigations for Acromegaly

A
  • Serum insulin-like growth factor 1 (IGF-1):elevated in acromegaly
    • As per Endocrine Society guidelines, this is thefirst-lineinvestigation for suspected acromegaly and, if elevated or inconclusive, an OGTT should be conducted to confirm the diagnosis; also used for monitoring
  • Oral glucose tolerance test (OGTT):
    • Physiologically, a glucose load should cause suppression of GH
    • In acromegaly, there isfailure of GH suppression2 hours post 75g glucose load (lack of suppression of GH to < 1 μg/L)
123
Q

Other investigations for Acromegaly

A

Pituitary MRI, Visual field tests, check pituitary hormone secretions for other hormones, CT other parts of body if ectopic suspected, GHRH levels check as will be elevated in hypothalamic cause

124
Q

Differential diagnosis for Acromegaly

A

Acromegaloidism or pseudo-acromegaly

125
Q

First line Management for Acromegaly

A

Surgery:trans-sphenoidal resection of the pituitary. Surgery isfirst-lineas acromegaly can have significant systemic complications

126
Q

Second line management for Acromegaly

A
  • Medical:for patients unsuitable for surgeryor if there are persistent symptoms after surgery
    • Dopamine agonists:used in mild disease; cabergoline is first-line (bromocriptine is an alternative) and has 30% efficacy
    • Somatostatin analogues:used in moderate to severe disease to directly inhibit GH release (e.g. octreotide); has an efficacy of 35-60%
    • GH antagonist:pegvisomant is also used in severe disease but, in reality, is often avoided due to cost; once-daily subcutaneous injection. Very effective and reduces IGF-1 in up to 95% of patients, but does not reduce tumour size so surgery is still required
127
Q

Third line management for Acromegaly

A

Radiotherapy:reserved for patients who have failed medical and surgical treatment, or in elderly patients unsuitable for surgery

128
Q

Monitoring for Acromegaly

A

Patients with acromegaly will require lifelong monitoring of growth hormone and insulin-like growth factor 1 (IGF-1) levels.

Once the initial treatment interventions (surgical, medical, and radiotherapy, as required) have remediated or significantly improved the disease state, regular monitoring of disease-related parameters is recommended.

Medical complications of acromegaly also require ongoing monitoring and treatment e.g. regular screening for colorectal cancer

129
Q

Complications of acromegaly

A

Cardiomyopathy, heart failure, hypertension, obstructive sleep apnoea, carpel tunnel, T2DM, Colorectal cancer, organ dysfunction, arthritis

130
Q

Prognosis of Acromegaly

A

The aim of treatment is biochemical normalisation of IGF-1 and random serum GH levels. Surgical treatment is curative, however, patients still need regular monitoring of GH and IGF-1 levels with life expectancy near normal in treated disease.

Acromegaly appears to be associated with an increased mortality. Much of this risk is related to the obstructive sleep apnea and cardiovascular complications. Studies have reported average survival reduction of up to 10 years in patients with acromegaly.

131
Q

Unique symptoms of gigantism

A

Late puberty, tall for age, reduced gonadal development

132
Q

Explain the difference between primary and secondary hyperaldosteronism

A

Primary: independant of RAAS, known as Conn’s syndrome

Secondary: dependant on RAAS

Both result in increased sodium retention and therefore water retention (increased BP)

133
Q

Epidemiology of Hyperaldosteronism

A
  • Primary hyperaldosteronism was originally thought to be rare, with a prevalence of <1%, but recent evidence suggests that it may be more common than initially thought.
  • Common in middle-aged adults
134
Q

Aetiology of Hyperaldosteronism

A
  • Primary hyperaldosteronismDescribes adrenal dysfunction causingraised aldosteronelevels withdecreased reninlevels due to negative feedback from sodium retention. Causes include:
    • Adrenal hyperplasia: idiopathic bilateral hyperplasia is the most common cause (⅔), can also be unilateral
    • Adrenal adenoma: classically termedConn’s syndrome
    • Adrenal carcinoma: extremely rare
    • Familial hyperaldosteronism: rare

Secondary hyperaldosteronism
Describes inappropriate activation of the RAAS, therefore patients haveraised aldosterone and raised reninlevels. Causes include:

- Renal artery stenosis
- Heart Failure: arterial hypovolemia due to reduced oncotic pressure causes reduced renal perfusion
135
Q

Risk factors for hyperaldosteronism

A
  • Family history of early onset hypertension
  • Family history of primary hyperaldosteronism
136
Q

Pathophysiology of hyperaldosteronism

A

Aldosterone is a mineralocorticoid and its role involves renal excretion of potassium and acid, as well as sodium reabsorption. The renin-angiotensin-aldosterone system (RAS) is activated in cases of hypovolemia and hyponatraemiaand leads to increased aldosterone levels with subsequent salt and water retention.

Classically, the disease presents as refractory hypertension, hypokalaemia, and metabolic alkalosis. Hypernatraemia may or may not be seen.

137
Q

Signs of hyperaldosteronism

A
  • Refractory hypertension
  • Hypokalaemia - increased K+ secretion by kidneys
  • Metabolic alkalosis - increased H+ secretion by kidneys
138
Q

Symptoms of hyperaldosteronism

A
  • Lethargy
  • Mood disturbance
  • Paresthesia and muscle cramps
  • Polyuria and nocturia
139
Q

1st line investigations for hyperaldosteronism

A

Aldosterone/renin ratio: first-line diagnostic test. Will show high aldosterone, with low renin in cases of primary hyperaldosteronism and high aldosterone and high renin in cases of secondary hyperaldosteronism.

CT imaging should be performed if there is a raised ratio.

140
Q

Other tests to order for hyperaldosteronism

A
  • Serum U&Es:hypokalaemia and hypernatraemia may be seen
    • Patients may have normal sodium levels due to the ‘aldosterone-escape’ mechanism
    • Water is absorbed alongside sodium which increases the hydrostatic pressure within peri-tubular capillaries causing sodium to leak back into the tubule
  • Blood gas - to look for alkalosis
  • High-resolution CT abdomen:useful to exclude carcinoma; if CT suggests an adenoma or hyperplasia, perform bilateral adrenal venous sampling
  • Adrenal venous sampling:to determine if there is unilateral or bilateral disease, and if the mass is functional
    • Adrenal vein sampling measures the amount of corticosteroid secreted from each adrenal gland
    • In a non-functional mass, imaging will show an abnormality but corticosteroid levels will be normal; removal would not be necessary in this instance
  • In cases of secondary hyperaldosteronism - doppler/ CT angio/ MRA to look for renal artery stenosis
141
Q

Differential diagnosis of hyperaldosteronism

A
  • Other forms of hypertension e.g.
    • Essential hypertension
    • Secondary hypertension
    • Liddle syndrome
142
Q

1st line management for hyperaldosteronism

A
  • Laparoscopic adrenalectomy:forunilateraladrenal hyperplasia or adenoma
  • Spironolactone:forbilateraladrenal hyperplasia or adenoma; spironolactone is an aldosterone antagonist
143
Q

2nd line management for hyperaldosteronism

A
  • In unilateral disease where surgery is inappropriate, treat with spironolactone
  • ENaC inhibitor: Amiloride, a potassium-sparing diuretic, may be used if aldosterone antagonists are not tolerated.
144
Q

Treatment for secondary hyperaldosteronism where renal arteries are involved

A

In secondary hyperaldosteronism - percutaneous renal artery angioplasty to resolve the renal artery stenosis

145
Q

Monitoring of hyperaldosteronism

A
  • Patients who have undergone unilateral adrenalectomy - BP, plasma electrolytes, and aldosterone and renin levels should be monitored every 6 to 12 months for clinical and biochemical evidence of recurrence (if cured postoperatively) or worsening (if improved but not cured) of PA.
  • Patients receiving aldosterone medications - Electrolytes and renal function should be monitored regularly (e.g., every 3 to 6 months), watching for development of hyperkalaemia, hyponatraemia, and uraemia. CT of the adrenals should be performed annually at first and, if no nodular growth is seen, every 3 to 4 years, indefinitely.
  • Patients with familial hyperaldosteronism type I (FH-I) - Hypertension is readily controlled by administering glucocorticoids in low doses. Control can be assessed by clinic, home, and ambulatory BP monitoring, and by periodic (e.g., yearly) echocardiography.
146
Q

Complications of hyperaldosteronism

A
  • Secondary to long-standing hypertension: ischaemic heart disease, stroke, hypertensive nephropathy and chronic kidney disease
  • Iatrogenic - hyperkalaemia
147
Q

Prognosis for hyperaldosteronism

A

Patients with primary hyperaldosteronism have increased mortality and cardiovascular morbidity compared to age and sex-matched controls. Surgical management leads to a cure in 50% of patients and the rest will have improvement of symptoms and blood pressure.

148
Q

Epidemiology of pituitary adenomas

A
  • Pituitary adenomas are the third most common intra-cranial neoplasms in adults, accounting for about 10% of all intra-cranial tumours.
  • The prevalence of pituitary adenoma varies from 19 to 28 cases per 100,000 in the UK
  • Prevalence increases with age - there is a peak in incidence between the ages of 30 to 60 years
149
Q

Risk factors for pituitary adenoma

A
  • MEN-1
  • Carney complex
  • Familial isolated pituitary adenomas - rare
150
Q

Pathophysiology of pituitary adenoma

A

Usually macroadenomas and can secrete a variety of hormones depending on the cell of origin

A number of cell lines may be affected:

  • Mammotrophs:Results in hyperprolactinaemia caused by a prolactinoma.
  • Somatotrophs:Acromegaly occurs due to excess growth hormone.
  • Corticotrophs:Results in the release of excess cortisol (Cushing’s syndrome) through excess production ofACTH.
151
Q

Clinical manifestations of pituitary adenomas

A

Symptoms will vary depending on cells affected and mass effects of the tumour

Prolactinoma
- Galactorrhoea
- Irregular menses
- Lack of libido
- Erectile dysfunction

Cushing’s related symptoms

Acromegaly related symptoms

Compressive effects
- Headache
- Visual disturbances - bitemporal hemianopia
- Palsy of cranial nerves III, IV, VI
- Diabetes insipidus
- May even present as hypopituitarism

152
Q

Investigations for pituitary adenoma

A

Those with a known family history (first and second-degree relatives) may be screened. Screening tends to be annual, typically from the ages of 5 to 65 (and may continue after this time, but less frequently).

  • Hormonal tests -
    • Prolactinoma:raised prolactin
    • Acromegaly: raised IGF-1 and failure of growth hormone suppression following oral glucose tolerance test
    • Other:the remaining hormones should also be screened as mass effect can lead to hypopituitarism.
  • Imaging -
    • MRI is 1st line
    • PET-CT
    • CT
  • DNA testing -MEN1: mutation testing should be offered to patients and their relatives
153
Q

Differential diagnosis for pituitary adenoma

A
  • Rathke’s cleft cyst: an abnormal fluid-filled (cyst) sac that usually is found between the anterior and posterior pituitary glands.
  • Craniopharyngioma: a rare type of noncancerous (benign) brain tumor that begins near the brain’s pituitary gland and can affect the function of the pituitary gland and other nearby structures in the brain.
  • Meningioma: a tumor that forms on membranes that cover the brain and spinal cord just inside the skull.
  • Hypophysitis: a rare condition which involves the acute or chronic inflammation of the pituitary gland or pituitary stalk.
  • Infection
154
Q

Management for Pituitary adenomas

A

Functioning tumours

  • Prolactinomas:first-line management is with dopamine agonists such as bromocriptine
  • Acromegaly/ Cushing’s:transsphenoidal resection is first-line

Non-functioning tumours
- Surgical resection:conducted when mass effect is observed

155
Q

Prognosis for pituitary adenoma

A

Patients with clinically non-functional pituitary adenomas (CNFPAs) generally have a good prognosis. The 10-year progression-free survival for pituitary adenoma is 80% to 94%.

Micro-adenomas do well with observation.

Macro-adenomas have a propensity to grow, and even when diagnosed as asymptomatic, need very close monitoring.

Patients with CNFPAs may be at increased risk of death, especially secondary to cardiovascular disease.

Patients with pituitary adenomas have been shown to have a lower quality of life (QoL) before and after pituitary surgery compared with people without pituitary adenomas.

156
Q

Define Addisons disease

A

Addison’s disease (primary adrenal insufficiency) is caused by destruction or dysfunction of the adrenal cortex.

Results in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and gonadocorticoid (androgens) deficiency

157
Q

Epidemiology of Addisons

A
  • In Europe, the overall prevalence has increased from 40-70 cases per million in the 1960s to more than 140 cases per million in developed countries.
  • More common in women
158
Q

Aetiology of Addisons

A
  • Autoimmune adrenalitis - most common in western world. Autoantibodies target the adrenal gland and the enzymes involved in steroid synthesis. One of the main targets for autoimmune destruction is the enzyme 21-hydroxylase.
  • Infection - TB (most common worldwide), HIV, Meningococcal infection
  • Congenital cause - congenital adrenal hyperplasia causes impaired cortisol synthesis
  • Medication
    • Long term steroid use (causes reduced ACTH via negative feedback)
    • Etomidate, Mitotane, Aminoglutethimide (reduce cortisol production) - drugs usually used to treat Cushing’s syndrome
  • Rare causes
    • Adrenal hemorrhage/ infarction
    • Malignant invasion
    • Infiltration of adrenal glands
      • Hemochromatosis
      • Amyloidosis
159
Q

Risk factors for Addisons

A
  • Female gender
  • Autoimmune conditions
  • Autoimmune polyendocrinopathy syndrome
  • Adrenal haemorrhage
  • Warfarin which may predispose to adrenal haemorrhage
  • TB
  • HIV
160
Q

Pathophysiology of Addisons

A

Addison’s disease refers tochronic primary adrenal insufficiency(hypoadrenalism) resulting in reduced adrenocortical hormones, including mineralocorticoids (zona glomerulosa), glucocorticoids (zona fasciculata), and androgens (zona reticularis).

Corticosteroids (glucocorticoids and mineralocorticoids) are involved in renal excretion of potassium and acid as well as sodium reabsorption. Hence, adrenal insufficiency results in ametabolic acidosiscoupled with hyperkalaemia and hyponatraemia.

In developed countries, such as the UK, most cases (80%) are caused byautoimmune destructionof the adrenal glands. These patients are at risk of developing other autoimmune conditions such as vitiligo or thyroid disease, and on occasion, forms part of an autoimmune polyendocrinopathy syndrome (APS).

Due to there not being any negative feedback, there are higher levels of CRH and ACTH.

161
Q

Signs of Addisons

A
  • Hyperpigmentation (caused by increased levels of ACTH) - especially in palmar creases and buccal mucosa
  • Vitiligo - due to loss of androgens
  • Loss of pubic hair in women
  • Hypotension and postural drop
  • Associated autoimmune conditions
  • Tachycardia
162
Q

Symptoms of Addisons

A
  • Lethargy and generalised weakness
  • Loss of libido
  • Nausea and vomiting
  • Cachexia - weight loss and muscle wasting
  • Dehydration
  • Salt-cravings
  • Collapse and shock (Addisonian crisis)
163
Q

1st line investigations for Addisons

A

8 - 9 am cortisol: NICE suggests using this first-line in primary care

  • <100 nmol/L: highly suggestive of Addison’s; NICE advise admission to hospital
  • 100 - 500 nmol/L: refer the patient for an ACTH stimulation test
  • > 500 nmol/L: Addison’s is unlikely; this result would be expected in normal people
164
Q

Gold standard tests for Addisons

A

ACTH stimulation test (short Synacthen test): Plasma cortisol is measured before and 30 minutes after giving Synacthen 250μg IM (ACTH analogue)

  • Failure of an adequate rise in cortisolpost-Synacthen (with peak cortisol levels < 500 nmol/L at 1 hour) suggests Addison’s disease
165
Q

Other investigations for Addisons

A
  • 8 am ACTH:increased due to loss of negative feedback from cortisol
  • Adrenal antibodies:anti-21-hydroxylase suggests autoimmune aetiology
  • U&Es:mineralocorticoid deficiency causeshyponatraemiaandhyperkalaemia
  • Aldosterone/renin ratio:decreased in Addison’s disease due to reduction in mineralocorticoid production
  • CT adrenal:atrophied glands in Addison’s disease; can also identify if malignancy is the cause
166
Q

Differentials for Addisons

A
  • Haemochromatosis due to hyperpigmentation
  • Hyperthyroidism due to weight loss and tachycardia
  • Anorexia nervosa due to weight loss
167
Q

1st line management for Addisons

A

Corticosteroid replacement:

  • Hydrocortisonein 2-3 doses divided throughout the day with a total dose of 20-30 mg for glucocorticoid replacement. Dose divisions vary in shift-workers with different sleep cycles; the largest dose is always given upon waking
  • Fludrocortisoneis recommended once daily for mineralocorticoid replacement (50-300 micrograms)
168
Q

Other management for Addisons

A
  • Androgen replacement - mainly in women
  • Patient education:
    • Patients should be advised regarding medication compliance and not missing doses
    • Advise patients to wear a MedicAlert bracelet or carry steroid cards in case of an Addisonian crisis
    • Advise patients todoubletheir glucocorticoid dose (hydrocortisone) if they develop an intercurrent illness
    • When travelling, patients should take extra medication plus an emergency hydrocortisone injection kit
169
Q

Monitoring for Addisons

A

Patients should be evaluated annually to judge adequacy of glucocorticoid and mineralocorticoid replacement. Dose can be adjusted depending on presentation of patients at review.

Monitoring also key due to complications associated with Addison’s disease.

170
Q

Addisons complications

A
  • Secondary Cushings due to excess hormone replacement
  • Osteopenia and osteoporosis
  • Secondary hypertension
  • Addisonian crisis - drop in glucocorticoid levels usually due to non-compliance with medication
171
Q

Addisons Prognosis

A

Addison’s disease is a lifelong illness. 40% of patients will experience an adrenal crisis. Overall, the mean age at death is 75.7 years (for females) and 64.8 years (for males), which is 3.2 and 11.2 years less than the estimated life expectancy.

172
Q

Define Addisonian crisis

A

Addisonian crisis, also known as an adrenal crisis, is a state of acute insufficiency of adrenocortical hormones. It most often occurs on a background of established Addison’s disease due to precipitating factors such as poor medication compliance, infection, trauma, surgery, and myocardial infarction.

173
Q

Epidemiology of Addisonian crisis

A

In those with Addison’s disease, 40% of patients will experience one crisis

174
Q

Aetiology of Addisonian crisis

A
  • Steroid withdrawal: any patient on long term steroids should not abruptly withdraw their medication
  • Severe dehydration
  • Sepsis or surgery: resulting in acute exacerbation of pre-existing adrenal insufficiency (e.g. Addison’s disease)
  • Meningococcal infection:meningococcal sepsis can lead to adrenal haemorrhage (Waterhouse-Friderichsen syndrome)
175
Q

Pathophysiology of Addisonian crisis

A

Drop in level of corticosteroids.

Corticosteroids (glucocorticoids and mineralocorticoids) are involved in renal excretion of potassium and acid as well as sodium reabsorption. Hence, adrenal insufficiency results in a metabolic acidosis coupled with hyperkalaemia and hyponatraemia. In a crisis, there is also accompanying haemodynamic instability due to sodium and, therefore, fluid loss.

176
Q

Signs of Addisonian crisis

A
  • Hypotension
  • Hypovolemic shock
  • Reduced GCS - consciousness
  • Confusion
  • Pyrexia - increased temperature
177
Q

Symptoms of Addisonian crisis

A
  • Nausea and vomiting
  • Abdo pain
  • Trigger e.g. infection or MI
178
Q

Investigations for Addisonian crisis

A
  • 12-lead ECG:hyperkalaemic changes include flat P waves, short QT interval, broad QRS, ST depression, and tented T waves
  • VBG:can be conducted quickly and will reveal metabolic acidosis with hyponatraemia and hyperkalaemia. Patients may also be hypoglycaemic
  • U&E’s: hyponatraemiaandhyperkalaemia; acute kidney injury may be present due to hypovolaemia causing pre-renal injury
  • FBC and CRP:leukocytosis and raised inflammatory markers may suggest an underlying infection as the precipitant
  • TFTs:hypothyroid states may mimic an Addisonian picture
179
Q

Management for Addisons

A
  • IV fluids: for resuscitation (e.g. normal saline); consider dextrose if hypoglycaemic
  • Corticosteroid:hydrocortisone100 mg IV (IM is an alternative) and a further dose 6 hours later may be given. Oral replacement usually starts after 24 hours, with a reduction to maintenance over 3-4 days
  • Fludrocortisone isnotrequired in the acute stage as hydrocortisone exerts an effect at the mineralocorticoid receptor
  • Treat the underlying cause e.g. infection
180
Q

Prognosis for Addisonian crisis

A

There are poor outcomes if treatment is delayed, with a risk of death due to hypovolaemic shock. Mortality is almost 100% if untreated

181
Q

Define Secondary adrenal insufficiency

A

Secondary adrenal insufficiency is adrenal hypofunction due to a lack of adrenocorticotropic hormone (ACTH).

Adrenal suppression refers to decreased cortisol production as a result of negative feedback on the hypothalamic-pituitary-adrenal axis, caused by excess glucocorticoids. The consequence is decreased production of both corticotropin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland, leading to a decrease in serum cortisol levels.

182
Q

Aetiology of secondary adrenal insufficiency

A
  • Iatrogenic - commonest cause. Due to long term steroid use leading to suppression of the HPA axis
  • Hypothalamic pituitary disease - resulting in reduced ACTH production
  • Removal of pituitary tumour - the remaining ACTH-secreting cells in the pituitary gland may be sluggish in their recovery, resulting in a period of adrenal suppression
183
Q

Pathophysiology of secondary adrenal insufficiency

A
  • Decreased levels of ACTH resulting in decreased glucocorticoid (CORTISOL)
  • Mineralocorticoid production remains intact
184
Q

Clinical manifestation of secondary adrenal insufficiency

A

Similar presentation to Addison’s disease.

However, no hyperpigmentation as there is no excess ACTH

185
Q

Investigations for secondary adrenal insufficiency

A

Same as with Addison’s disease

  • ACTH levels are low and mineralocorticoid production is intact in secondary hypoadrenalism - can be used to differentiate from Addison’s
186
Q

Management for secondary adrenal insufficiency

A
  • Adrenals will recover if long-term steroids are slowly weaned off - but this is
    a long and difficult process
  • ORAL HYDROCORTISONE - replacement of glucocorticoids
187
Q

Prognosis for secondary adrenal insufficiency

A

Adrenal insufficiency secondary to corticosteroid treatment has a generally good prognosis. Time to recovery depends on dose and/or potency of glucocorticoid used and treatment length. Signs and symptoms of Cushing’s syndrome will disappear with time as the inciting medication is stopped.

188
Q

ADH physiology

A

Antidiuretic hormone (ADH) is produced by the magnocellular neurons in the paraventricular and supraoptic nuclei of the hypothalamus.

It is stored and released by the posterior pituitary in response to rising plasma osmolality or decreasing blood volume. It may also be referred to as arginine vasopressin (AVP) or simply vasopressin.

ADH acts on the distal convoluted tubule and collecting duct to increase water reabsorption independent of sodium. ADH stimulates the insertion of aquaporin-2 channels onto the luminal membrane, allowing the free entry of water. ADH also causes vasoconstriction of arterioles.

189
Q

Define SIADH

A

The syndrome of inappropriate anti-diuretic hormone (SIADH) results from excess ADH secretion.

ADH excess, as the name suggests, results in reduced diuresis - water excretion and urinary output are reduced. This leads to an increase in total body water and hyponatraemia.

190
Q

Epidemiology of SIADH

A
  • Hyponatraemia is the most common electrolyte disorder encountered in clinical practice
  • The prevalence of hyponatraemia in the community is around 8% and increases with age (approximately 12% in people aged 75 or older)
191
Q

Aetiology of SIADH

A
  • Neurological
    • Meningitis, encephalitis or cerebral abscess
    • Intracranial haemorrhage, e.g. subarachnoid or subdural haemorrhage
    • Stroke
    • Trauma
  • Malignancy
    • Small cell carcinoma of the lung most commonly
    • Other cancers, e.g. breast cancer, and head and neck tumours, are rarer causes
  • Infections
    • Pneumonia
    • Tuberculosis
    • HIV
  • Endocrine
    • Hypothyroidism
    • Hypopituitarism
  • Drugs (remember mnemonic CARDISH - chemo, antidepressants, recreational drugs, diuretics, inhibitors e.g. ACEI & SSRIs, sulfonylurea, hormones e.g. desmopressin)**
    • SSRIs and TCAs
    • Proton pump inhibitors
    • Carbamazepine
    • Cyclophosphamide
    • Sulfonylureas (glimepiride and glipizide)
192
Q

Risk factors for SIADH

A
  • Age >50
  • Pulmonary conditions
  • Malignancy
  • Medicine associated with SIADH induction
  • CNS disorder
193
Q

Pathophysiology of SIADH

A

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) describesincreased antidiuretic hormone(ADH)releasefrom the posterior pituitary or an ectopic source.

ADHis responsible for free water reabsorption by acting on the collecting ducts of the kidney, resulting inwater retention by increased insertion of aquaporin 2, butnotthe reabsorption of solutes. This increases blood volume and decreases serum osmolarity.

Increased ADHresults in increased free water retention, subsequent dilution of the blood and a decrease in solutes in the blood.

Increase in blood volume leads to stretching of heart muscle and release of ANP and BNP(natriuretic peptide). This inhibits renin release and activity, and therefore the RAAS system. This promotes natriuresis (excretion of sodium). This leads to sodium and water excretion, which promotes further ADH activity.

This cycle continues. Overtime, the kidneys will adapt. The number of aquaporin channels will decrease to compensate for the amount of ADH present. This will now lead to diuresis as well as natriuresis. This is why there is there is a euvolaemic state rather than a hypervolaemic state, coupled with hyponatraemia.

Overall, patients will have high urine Na+ levels and low serum Na+ levels. They will be euvolaemic due to compensatory mechanisms.

194
Q

Key features of SIADH

A

Hyponatraemic and euvolaemic (no features of hyper- or hypovolaemia)

195
Q

Symptoms of SIADH

A

Mild(130-135 mmol/L):

  • Nausea, vomiting, headache, lethargy, anorexia

Moderate(125-129 mmol/L):

  • Weakness, muscle aches, confusion, ataxia, asterixis

Severe(< 125 mmol/L):

  • Reduced consciousness, seizures, myoclonus, respiratory arrest
196
Q

Investigations for SIADH

A

There is no single test that conclusively diagnoses SIADH. Instead, diagnosis relies upon suggestive biochemistry results and the clinical context.

Blood tests

Renal function: gives a serum sodium that confirms hyponatraemia. May also show a low serum urea consistent with mild volume expansion.

Serum osmolality: a low serum osmolality is seen, less than 280 mOsm/kg.

Urinary tests

Urinary osmolality: a high urine osmalality is seen, greater than 100 mOsm/kg.

Urine sodium: typically a high urinary sodium is seen, greater than >40 mmol/L.

197
Q

Diagnostic criteria for SIADH

A
  • Low plasma osmolality: < 275 mOsm/kg
  • High urine osmolality: > 100 mOsm/kg
  • High urine sodium: > 30 mmol/L
  • Clinical euvolaemia
  • Exclusion of glucocorticoid deficiency or hypothyroidism(rare)
198
Q

Management for SIADH

A

Treat underlying cause

  • Acute management: <48 hrs onset
    Acute hyponatraemia must be treated urgently due to the risk of cerebral oedemaand herniation
    • Hypertonic (3%) salineis preferred - slow infusion to avoid complications
    • Furosemide (diuretic) - in patients who have fluid overload. Causes an increase in water, Na+, Ka+ and Cl- excretion. (Note: KCl should be replaced)

Chronic management:
- Correction should not occur too quickly and aim for amaximum increase in 10 mmol/L per day
- Mild to moderate asymptomatic cases: fluid restriction to increase Na+ conc
- Fluid restriction may not be used in SIADH secondary to subarachnoid haemorrhage as it risks lowering blood pressure which may cause cerebral vasospasm and infarction.
- Severe or symptomatic cases: guidelines differ but demeclocycline or tolvaptan may be considered
- Demeclocycline, a tetracycline antibiotic, causes an iatrogenic nephrogenic diabetes insipidus through the inhibition of ADH. Though historically popular it is rarely used today.
- A newer class of drugs termedvaptans(e.g. tolvaptan) are now more commonly used. These ADH receptor antagonists are effective but expensive agents.

199
Q

Complications of SIADH

A
  • Cerebral oedema: hyponatraemia lowers the osmolality of the blood causing an osmotic shift of water into brain tissue with subsequent oedema and risk of herniation
  • Central pontine myelinolysis:rapid correction of sodium can cause osmotic demyelination, particularly in chronic hyponatraemia (slow correction is vital)
    • Manifests as tremors, dysarthria, quadriplegia, ophthalmoplegia, seizures and extrapyramidal symptoms
    • May result in ‘locked-in syndrome’, where patients are awake but unable to verbally communicate or move
    • Diagnosis is confirmed with MRI
200
Q

Prognosis for SIADH

A

If the underlying cause is found and treated successfully, SIADH typically resolves. If the underlying condition persists, SIADH is difficult to manage, secondary to difficulty complying with necessary fluid restriction or medicines.

201
Q

Explain potassium homeostasis

A

Potassium homeostasis is multifactorial and depends on intake, absorption, distribution, and excretion. Important hormonal factors that reduce serum potassium include insulin (causes an intracellular shift of potassium), adrenaline (beta-receptor stimulation causes intracellular shift), and aldosterone (promotes potassium excretion).

202
Q

Define hyperkalaemia

A

A serum level >5.5 mmol/L is considered to be hyperkalaemia

A serum level > 6.5mmol/L = MEDICAL EMERGENCY!

203
Q

Aetiology of hyperkalaemia

A
  • Decreased excretion:
    • Acute kidney injury (AKI) or oliguric renal failure (where there is very small amount of urine produced) - COMMON
  • Drugs:
    • Potassium-sparing diuretics e.g. spironolactone - COMMON
    • ACE inhibitors (interfere with RAAS) e.g. ramipril - COMMON
    • NSAIDs - COMMON
    • Ciclosporin
    • Heparin
    • Beta-antagonists: inhibit cellular entry of potassium
    • Digoxin: inhibitor of Na+/K+ ATPase causing reduced cellular entry of potassium
  • Addison’s disease - reduced aldosterone causes reduced potassium excretion
  • Redistribution of K+ - intracellular to extracellular:
    • Diabetic ketoacidosis - insulin resistance - insulin controls Na+/K+ pump - pumping sodium out of cell in exchange for K+. With insulin resistance, the K+ leaves the cell.
    • Metabolic acidosis - to compensate H+ is pumped into cell from the blood, in exchange of K+
    • Tissue necrosis or lysis
    • Rhabdomyolysis - muscle breakdown releases potassium
  • Death of muscle fibres and release of their contents, including K+, into bloodstream caused by a traumatic CRUSH INJURY e.g. from a car accident or building collapse
    • Tumour lysis syndrome
    • Severe burns
  • Increased load:
    • Potassium chloride
    • Transfusion of stored blood
204
Q

Pathophysiology of hyperkalaemia

A
  • The amount K+ in the blood determines the excitability of nerve and muscle cells, including skeletal muscle, smooth muscle and cardiac muscle
  • When K+ levels in the blood rise - this reduces the difference in electrical potential between cardiac myocytes and outside of the cells meaning the threshold for action potential is significantly decreased resulting in increased abnormal action potential and thus abnormal heart rhythms that can result in ventricular fibrillation and cardiac arrest
  • In smooth muscle it can cause cramping - due to depolarisation and contraction
  • In skeletal muscle it can cause weakness and flaccid paralysis - resting potential is too high, which means muscle can’t repolarise and then contract again
  • In cardiac muscle it can cause arrhythmias or even cardiac arrest
205
Q

Signs of hyperkalaemia

A
  • Tachycardia (arrhythmia)
  • Fast irregular pulse
  • ECG differences - tall tented T waves, small P waves, wide QRS
206
Q

Symptoms of hyperkalaemia

A
  • Muscle weakness
  • Lightheadedness
  • Muscle cramps
  • Paresthesia (tingling in skin)
  • Palpitations
  • Chest pain
207
Q

Investigations for hyperkalaemia

A
  • 12-lead ECG:hyperkalaemic changes include flat P waves, short QT interval, broad QRS, ST depression, and tented T waves
  • U&Es:confirm high serum potassium levels
  • Lithium heparin sample:rule out pseudohyperkalaemia. This is where thrombus formation and haemolysis within a normal EDTA tube can cause a falsely elevated potassium concentration; e.g. when the tourniquet is too tight or blood is left sitting too long
  • VBG:check for acidosis which may be causing the hyperkalaemia
208
Q

Differentials for hyperkalaemia

A
  • Could be artefactual - repeat tests if pt has no symptoms
    • Haemolysis e.g. from vigorous venepuncture or due to K+ release from abnormal RBCs in some blood disorders e.g. leukaemia
    • Contamination with K+ EDTA anticoagulant in FBC bottles
    • Thrombocythaemia (increased platelets) - K+ leaks out of platelets during clotting
  • DKA
  • Hyperosmolar hyperglycaemic state
  • Chronic kidney disease
209
Q

Urgent Management for hyperkalaemia

A

If there are signs of myocardial hyperexcitability and serum levels > 6.5mmmol/L

  • Cardiac membrane protection:if ECG changes are present, 10ml of 10% IV calcium gluconate or calcium chloride should be givenimmediately. If ECG changes arenotpresent this should not be given, regardless of the serum concentration
    • Calcium protects the cardiac membrane but its effects are short-lived and may need repeating after 5 minutes if ECG changes persist (repeat ECGs are required)
    • It doesnotlower potassium concentration
  • Potassium reduction:
    • Insulin/dextrose infusion: causes anintracellular shiftof potassium; the dose is 10 units actrapid with 50 ml of 50% glucose over 15 mins
    • Nebulised salbutamol: causes anintracellular shiftof potassium
210
Q

Non-urgent management for hyperkalaemia

A
  • Treat underlying cause
  • Review medication
  • Can give polystyrene sulfonate resin (calcium resonium) which binds K+ in the gut and thus reduces absorption
211
Q

Other treatment for hyperkalaemia

A
  • Haemodialysis: removes potassium from the body
  • Enema - if vomiting prevents calcium resonium administration
212
Q

Complications of hyperkalaemia

A

Cardiac arrhythmias and arrest: severe hyperkalaemia is associated with broadening of the QRS complex and can cause potentially life-threatening ventricular tachycardia or ventricular fibrillation, and subsequent cardiac arrest

213
Q

Prognosis for hyperkalaemia

A

The prognosis of patients with hyperkalaemia ultimately depends on the underlying cause. Untreated moderate and severe hyperkalaemia is associated with the development of potentially life-threatening arrhythmias so must be treated expediently.

214
Q

Define hypokalaemia

A

Potassium is an essential body cation, which has a normal plasma concentration of 3.5-5.5 mmol/L. Hypokalaemia is defined as a plasma potassium concentration < 3.5 mmol/L.

Hypokalaemia can be further divided as follows:

  • Mild:3.0-3.4 mmol/L
  • Moderate:2.5-2.9 mmol/L
  • Severe:< 2.5 mmol/L or symptomatic
215
Q

Epidemiology of hypokalaemia

A
  • Hypokalaemia is a common electrolyte abnormality in secondary care affecting up to 20% of inpatients.
  • Potassium concentration is highly variable depending on age, sex, ethnicity and socioeconomic status.
216
Q

Aetiology of hypokalaemia

A
  • Inadequate intake
    • Eating disorders: bulimia, anorexia nervosa, alcoholism
    • Poor diet
    • Systemic illness and dental problems
    • Inadequate potassium in feed or fluid replacement (IVF, NG feed, TPN)
  • Increased excretion
    • Renal tubular failure
    • Diuretics (thiazide-like & loop)
    • Mineralocorticoid excess e.g.
      • Cushing’s syndrome
      • Conn’s syndrome
      • Nephrotic syndrome - leaky kidneys resulting in increased aldosterone secretion and thus K+ loss
      • Steroid use causing mineralocorticoid excess
    • Genetic causes include:Bartter’s syndrome:Refers to a group of autosomal recessive conditionscharacterised by hypokalaemia, alkalosis, and hypotension or normotension, related to genetic variants in genes encoding proteins in the loop of Henle.Gitelman’ssyndrome:Is an autosomal recessive condition characterised by hypokalaemia, hypomagnesaemia, alkalosis, and hypotension or normotension, related to a genetic variant in a gene encoding the thiazide-sensitive sodium chloride transporter.Liddle’ssyndrome:Is an autosomal recessive condition characterised by hypokalaemia and hypertension, related to genetic variants in genes encoding the subunits of the epithelial sodium channel.
    • Gastrointestinal: diarrhoea, vomiting, pyloric stenosis, villous adenoma, laxative abuse
    • Skin: burns, erythroderma, hyperhidrosis
  • Shift from extracellular to intracellular K+
    • Alkalosis - H+ moves out of cell and is swapped for K+ as a compensatory mechanism
    • Insulin excess - Na+/K+ pump, more K+ moves into cell
    • Activation of beta-adrenergic receptors (e.g. salbutamol) enhance movement of K+ intracellularly.
217
Q

Pathophysiology of hypokalaemia

A

K+ key for maintaining resting cell membrane potential

Low levels of K+ can affect smooth, skeletal and cardiac muscles due to diminished contraction

  • Cardiac - arrhythmias and cardiac arrest
  • Smooth muscle - constipation
  • Skeletal muscle - weakness, cramps and flaccid paralysis
  • Respiratory muscles - respiratory depression
218
Q

Signs of hypokalameia

A
  • Arrhythmias
  • Muscle paralysis and rhabdomyolysis (severe)
  • Hypotonia - decreased muscle tone
  • Hypoflexia - muscles less responsive to stimuli
219
Q

Symptoms of hypokalaemia

A
  • Fatigue
  • Generalised weakness
  • Light headedness
  • Muscle cramps and pain
  • Tetany
  • Palpitations
  • Constipation
220
Q

1st line investigations for hypokalaemia

A

The diagnosis of hypokalaemia is based on a laboratory sample of plasma potassium:

  • Mild:3.0-3.4 mmol/L
  • Moderate:2.5-2.9 mmol/L
  • Severe:< 2.5 mmol/L or symptomatic
221
Q

Other investigations for hypokalaemia

A
  • ECG - Prolonged PR, ST segment depression, flattening of T wave, U wave present
  • Urine osmolality
  • Urinary electrolytes (sodium & potassium)
  • Full blood count
  • U&Es, bone profile, magnesium
  • VBG/ABG (can assess acid/base, bicarbonate & chloride)
  • CK (creatinine kinase) - sign of muscle damage
222
Q

Management for mild/moderate hypokalaemia

A
  • Treat underlying cause
  • Review medication
    • If taking a diuretic, replace with a potassium sparing diuretic
  • Other electrolyte abnormalities, magnesium in particular, should be identified and replaced. Hypokalaemia difficult to treat until Mg2+ levels have been normalised.
  • Potassium replacement -
    • Oral route preferred
    • e.g. SANDO-K (potassium chloride with potassium bicarbonate), two tablets, three times a day for mild hypokalaemia and two tablets, four times a day for moderate hypokalaemia.
223
Q

Management for severe hypokalaemia

A
  • IV replacement with 40 mmol of KCL in 1 litre of normal saline. The maximal rate on a normal ward is 10 mmol of potassium an hour. A repeat blood test should be sent after each bag of replacement.
  • In rare cases it may be necessary to give more concentrated replacement (e.g. 40 mmol KCL in 500ml of normal saline or 10 mmol KCL in 100 mls of normal saline) or more rapid replacement. This should only be done under the guidance of a senior physician in compliance with local guidelines, normally in an HDU/ITU setting.
  • Do not give K+ if oliguric
  • Never give K+ as a fast stat bolus dose
224
Q

Complications of hypokalameia

A

Cardiac - arrhythmias and cardiac arrest

225
Q

Define diabetes insipidus

A

Diabetes insipidus (DI) is a metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine.

It is due to the patient’s inability to make ADH or respond to ADH. This leads to polydipsia, polyuria, and hypotonic urine.

226
Q

Epidemiology of DI

A
  • DI is uncommon, although the exact prevalence is difficult to estimate.
  • There are no differences in prevalence between sexes or among ethnic groups.
  • Inherited causes for both central and nephrogenic DI account for less than 10% of all cases.
227
Q

Aetiology of DI

A
  • Nephrogenic - pathology affecting the kidney
    • Drugs e.g. Lithium, Demeclocycline
    • Genetic - AVR2 gene X chromosome
    • Intrinsic kidney disease
    • Post-obstructive uropathy - urine can’t flow due to obstruction and so refluxes back into kidney
    • Electrolyte imbalances - mainly hypokalaemia and hypercalcaemia
  • Cranial - ADH not produced or secreted
    • Idiopathic
    • Congenital defects in ADH gene
    • Brain tumours
    • Head injuries
    • Brain malformations
    • Hypophysitis
    • Hypophysectomy
    • Infections e.g. meningitis, encephalitis, TB
    • Infiltration e.g. sarcoidosis
    • Brain surgery
    • Radiotherapy
228
Q

Risk factors for DI

A
  • Pituitary surgery
  • Craniopharyngioma
  • Brain injury
  • Congenital pituitary abnormalities
  • Medication e.g. lithium
  • Autoimmune disease - some cases linked to antibodies against ADH secreting cells
  • Family history
  • CNS infections
  • Pregnancy - associated with a number of changes in salt and water regulation. A transient central DI may develop as a consequence of a decreased osmotic threshold for thirst and ADH release, and a decrease in plasma osmolality. Also associated with increase in metabolic clearance of ADH.
229
Q

Pathophysiology of DI

A
  • Central DI results from any condition that impairs the production, transportation, or release of ADH.
  • Nephrogenic DI results from conditions that impair the renal collecting ducts’ ability to respond to ADH.

Both central and nephrogenic DI are characterised by impaired renal water re-absorption, resulting in the production of excessive, hypotonic (dilute) urine (polyuria). This is accompanied by significant thirst and increased drinking (polydipsia), as central osmo-sensing and peripheral baro-sensing drive central thirst and thirst-dependent behaviours to maintain circulating volume and osmolar status.

230
Q

Signs of DI

A
  • Postural hypotension
  • Hypernatraemia
231
Q

Symptoms of DI

A
  • Polyuria
  • Polydipsia
  • Dehydration
232
Q

1st line investigations for DI

A
  • U&E - hypernatraemia found
  • Serum glucose - exclude DM
  • Urine osmolality - low urine osmolality found
  • Serum osmolality - high serum osmolality found
  • Water deprivation test (desmopressin suppression test) - avoid taking fluid or foods 8 hrs before test. Then urine osmolality is measured followed by giving desmopressin. 8 hrs later urine osmolality is measured again. Allows us to differentiate between cranial and nephrogenic diabetes insipidus
    • Cranial - ADH not being made but kidney’s still able to respond. So when desmopressin is given, urine osmolality should increase. In nephrogenic causes, desmopressin will not have an effect on urine osmolality after synthetic desmopressin administration.`
233
Q

Gold standard test for DI

A

Water deprivation test (desmopressin suppression test)

234
Q

Other tests for DI

A

MRI - for cranial DI. Test anterior pituitary function.

235
Q

Differentials for DI

A
  • Primary polydipsia - normal ADH, but excessive thirst and excessive urine production. In the water deprivation test, patient’s with primary polydipsia will already have high urine osmolality prior to desmopressin administration.
  • Diabetes mellitus - due to polyuria and polydipsia
  • Hypercalcaemia
236
Q

1st line management for DI

A
  • Correct underlying cause
  • Mild cases can be managed conservatively e.g. low sodium diet
  • Desmopressin
    • Used in cranial DI to replace ADH
    • Can be used in nephrogenic DI at very high doses. This needs monitoring
  • Thiazide diuretic e.g. Bendroflumethiazide for nephrogenic DI - will produce a mild hypovolaemia which will encourage the kidneys to take up more Na+ and water in the proximal tubule, thereby offsetting water losses
237
Q

Other management for DI

A

NSAIDs - can be used in nephrogenic DI. Prostaglandins locally inhibit ADH action. NSAID’s lower urine volume and plasma Na+ by inhibiting prostaglandin synthase.

238
Q

Emergency management for DI

A
  • Urgent plasma U&E, serum and urine osmolality
  • IV fluid to keep up with urine output. If severe hypernatraemia, do not lower Na+ rapidly. Risk of cerebral oedema with rapid correction!
  • IM desmopressin
239
Q

Monitoring for DI

A

Patients require regular follow-up with monitoring of serum electrolytes to assess sodium status.

For patients with central DI, follow-up imaging is recommended if initial scans were unable to detect pathology, as pituitary, para-pituitary, or stalk lesions may not manifest on initial scanning.

In patients with nephrogenic DI for whom polyuria is significant, bladder dysfunction may develop. If unrecognised, this may lead to renal impairment. These patients need periodic renal and bladder ultrasonography and regular assessment of serum creatinine.

240
Q

Prognosis for DI

A

Outcome and outlook depend on the underlying aetiology, type of DI, and associated comorbidities.

  • While DI is often a lifelong condition, central DI following pituitary surgery or traumatic brain injury may be transient.
  • Nephrogenic DI secondary to hypercalcaemia or hypokalaemia commonly resolves following treatment of the underlying electrolyte disorder. While nephrogenic DI secondary to medication may resolve following agent discontinuation, this is often not the case in those with nephrogenic DI secondary to lithium.
  • DI developing in pregnancy typically resolves following delivery.
241
Q

Action of PTH

A

Parathyroid hormone:

Changes in the body’s levels of extracellular calcium are detected by the calcium-sensing receptor in parathyroid cells. There are four parathyroid glands situated in four corners of the thyroid gland. The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to hypocalcaemia (low blood calcium).

The parathyroid hormone causes:

  • The bones to release calcium
  • The kidneys to reabsorb more calcium so it’s not lost in the urine (as well as excrete more phosphate)
  • The kidneys to synthesise calcitriol/ active Vitamin D. Active Vitamin D then goes on to cause the gastrointestinal tract to increase calcium absorption.
242
Q

Define Hypercalcaemia

A

Hypercalcemia refers to a higher than normal calcium levels in the blood, generally over 10.5 mg/dL.

243
Q

Aetiology of hypercalcaemia

A
  • Acidosis: promotes less binding between albumin and calcium. This causes less bound calcium and more free ionised calcium
  • Osteoclastic bone resorption due to:
    • Hyperparathyroidism
    • Malignant tumours: secrete parathyroid hormone-related protein or PTHrP, a hormone that mimics the effect of parathyroid hormone which stimulates the osteoclasts and cause osteoblasts to die
  • Excess vitamin D: increased calcium absorption from GI tract
  • Sarcoidosis: due to the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages
  • Thyrotoxicosis: thyroid hormones known to cause bone resorption
  • Milk-alkali syndrome: ingestion of large amounts of calcium and absorbable alkali, with resulting hypercalcemia.
  • Medications
    • Thiazide diuretics increases calcium reabsorption in the distal tubule of the kidney
    • Lithium
  • Familial benign hypocalciuric hypercalcaemia: defect in calcium sensing receptor
244
Q

Pathophysiology of hypercalcaemia

A

High levels of ionised calcium affect a variety of cellular processes, in particular, electrically active neurons.

With high levels of extracellular calcium, voltage-gated sodium channels are less likely to open up, which makes it harder to reach depolarisation, and makes the neuron less excitable.

  • This causes slower or absent reflexes
  • The sluggish firing of neurons also leads to slower muscle contraction, which causes constipation and generalised muscle weakness.
  • In the central nervous system, hypercalcaemia causes confusion, hallucinations, and stupor.

Too much calcium in the blood causes hypercalciuria. This leads to a loss of excess fluid in the kidneys causing an individual to get dehydrated.

245
Q

Clinical manifestations of hypercalcaemia

A
  • Abdominal pain
  • Vomiting
  • Constipation
  • Dehydration
  • Polydipsia
  • Polyuria
  • Absent reflexes
  • Muscle weakness
  • Weight loss
  • Depression
  • Confusion
  • Hallucinations
  • Stupor
  • Hypertension
  • Pyrexia
246
Q

Investigations for hypercalceamia

A
  • Bloods: high calcium. Also check parathyroid hormone, vitamin D, albumin, phosphorus, and magnesium levels.
    • In malignancy, there is low albumin, low chloride, alkalosis, low potassium, high phosphate, high ALP
    • Hyperparathyroidism: high PTH
  • 24 hr urinary Ca2+ excretion: raised
  • Electocardiogram: tachycardia, AV block, shortening of the QT interval, and sometimes in the precordial leads the appearance of an J wave
  • Imaging
    • Chest X-ray
    • Isotope bone scan
247
Q

Differentials for hypercalcaemia

A

Hyperalbuminaemia (pseudohypocalcaemia): causes there to be a higher concentration of protein-bound calcium, while free ionised calcium concentrations stay the same. This can occur when individuals are dehydrated, concentrating albumin.

248
Q

Management for hypercalcaemia

A
  • Increase urinary calcium excretion
    • Rehydration: increases filtering of Ca2+
    • Loop diuretics: inhibit calcium reabsorption in the loop of Henle
  • Decrease calcium absorption from GI tract
    • Glucocorticoids
  • Prevention of bone resorption
    • Biphosphonates
    • Calcitonin
  • Chemotherapy may help in malignancy
249
Q

Complications of Hypercalcaemia

A
  • Kidney stones: due to dehydration combined with hypercalciuria
  • Renal failure
  • Ectopic calcification e.g. cornea
  • Cardiac arrest
250
Q

Define Hypocalcaemia

A

Hypocalcemia refers to lower than normal calcium levels in the blood, generally less than 8.5 mg/dL.

251
Q

Aetiology of Hypocalcaemia

A

With increased phosphate:

  • Chronic kidney disease: lack of reabsorption of Ca2+, lack of active vitamin D
  • Hypoparathyroidism: e.g. due to removal of or autoimmune destruction PT glands, DiGeorge syndrome
  • Pseudohypoparathyroidism
  • Acute rhabdomyolysis: large numbers of cells die and release phosphate. The phosphate binds to the ionised calcium and forms calcium phosphate, making it insoluble and effectively decreasing the total amount in blood.
  • Hypomagnesaemia: magnesium is needed for PTH secretion

With normal or low phosphate:

  • Vitamin D deficiency: leads to less Ca2+ absorption from GI tract
  • Osteomalacia
  • Acute pancreatitis: free fatty acids end up binding to ionised calcium, which is insoluble and precipitates.
  • Over-hydration
  • Respiratory alkalosis: high pH (alkalosis) causes more binding between albumin and calcium, which results in less free ionised calcium
252
Q

Pathophysiology of Hypocalcaemia

A

Low levels of ionised calcium affect a variety of cellular processes e.g.

  • With low levels of extracellular calcium, voltage-gated sodium channels are less stable and more likely to open up, which allows the cell to depolarise more easily, and makes the neurone more excitable. This can trigger tetany.
253
Q

Clinical Manifestations of Hypocalcaemia

A

SPASMODIC:

  • Spasms (Trousseau’s sign): blood pressure cuff occludes the brachial artery, and that pressure on the nerve is enough to make it fire, which results in a muscle spasm that makes the wrist and metacarpophalangeal joints flex.
  • Perioral numbness/ paraesthesiae
  • Anxious, irritable, irrational
  • Seizures
  • Muscle tone increases: colic, wheeze and dysphagia
  • Orientation impaired and confusion
  • Dermatitis
  • Impetigo herpetiformis (severe pustular psoriasis occurring in pregnancy)
  • Chvosteks sign (facial muscles twitch after the facial nerve is lightly finger tapped); choreoathetosis, cataract (if chronic hypocalcaemia), cardiomyopathy
254
Q

Investigations for Hypocalcaemia

A
  • Bloods: low calcium. Also check for parathyroid hormone, vitamin D, albumin, phosphorus, and magnesium levels.
  • Electrocardiogram: may show prolonged QT, prolonged ST segment, and arrhythmias e.g. torsade de pointes and atrial fibrillation.
255
Q

Differentials for hypocalcaemia

A

Hypoalbuminaemia (pseudohypocalcaemia): there is a loss of bound calcium but free ionised levels remain the same

256
Q

Management for hypocalcaemia

A
  • Calcium supplements e.g. calcium gluconate
  • Vitamin D supplementation e.g. alfacalcidol, if appropriate
  • If alkalosis, correct alkalosis
257
Q

Define Hyperparathyroidism

A

Hyperparathyroidism refers to a condition where there is an overproduction of parathyroid hormone.

258
Q

Pathophysiology of Primary hyperparathyroidism

A

Caused by uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands (independent of calcium levels). This leads to hypercalcaemia.

Most often, primary hyperparathyroidism is caused by a single parathyroid adenoma which happens either because of a genetic mutation in a single cell or because of an inherited disorder e.g. multiple endocrine neoplasia.

Rarely, primary hyperparathyroidism is caused by hyperplasia or by a parathyroid carcinoma.

259
Q

Pathophysiology of secondary hyperparathyroidism

A

Insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones. This causes hypocalcaemia. This is usually due to kidney issues as the kidney can’t filter out the phosphate or make active vitamin D.

The parathyroid glands reacts to the low serum calcium by excreting more parathyroid hormone. Over time the total number of cells in the parathyroid glands increase as they respond to the increased need to produce parathyroid hormone. The glands become more bulky.

The serum calcium level will be low or normal but the parathyroid hormone will be high.

260
Q

Pathophysiology of tertiary hyperparathyroidism

A

This happen when secondary hyperparathyroidism continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of parathyroid hormone increases dramatically.

Then when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. This high level of parathyroid hormone in the absence of the previous pathology leads to high absorption of calcium in the intestines, kidneys and bones and causes hypercalcaemia.

261
Q

Hypercalcaemia vs Hypercalciuria

A

Hypercalcaemia:

  • Excess calcium makes neurons less excitable, which leads to slower muscle contractions, and diminishes neuron firing in the central nervous system.

Hypercalciuria:

  • This is because there is just too much calcium to be reabsorbed by the kidneys. Excess loss of calcium in urine can lead to dehydration.
262
Q

Clinical manifestations of hyperparathyroidism

A

‘Stones, thrones, bones, groans, and psychiatric overtones’

  • Stones: kidney stones or gallstones
  • Thrones: refers to the toilet, polyuria that results from impaired sodium and water reabsorption.
  • Bones: bone pain
  • Groans: refers to symptoms of constipation, nausea and vomiting
  • Psychiatric overtones: depressed mood, fatigue, psychosis and confusion
263
Q

Investigations for hyperparathyroidism

A

Bloods: high levels of parathyroid hormone; testing for blood levels of calcium, phosphate, and vitamin D to confirm the type of hyperparathyroidism.
- 24 hr urinary calcium: raised
- ALP: raised from bone activity

264
Q

Other investigations for hyperparathyroidism

A

Imaging e.g.

  • DEXA scan for osteoporosis
  • Can show osteitis fibrosa cystica
265
Q

Differential for hyperparathyroidism

A

Malignant hyperparathyroidism: parathyroid related protein produced by some squamous cell lung cancers, breast and renal cell carcinomas. This can mimic PTH and lead to hypercalcaemia.

266
Q

Management for primary hyperparathyroidism

A
  • If mild, increase fluid intake, avoid thiazides and high Ca2+ intake
  • Surgical removal of the tumour
  • Calcimimetics: drugs that imitate the action of calcium by attaching to the calcium-sensing receptors on parathyroid cells
267
Q

Secondary hyperparathyroidism management

A
  • Correcting the vitamin D deficiency
  • Phosphate binders
  • Renal transplant to treat renal failure
  • Sometimes parathyroidectomy
268
Q

Management for tertiary hyperparathyroidism

A

Surgical removal of parathyroid tissue

269
Q

Complications of all types of hyperparathyroidism

A
  • Secondary hyperparathyroidism can cause:
    • Renal osteodystrophy: bone resorption
  • Secondary and tertiary hyperparathyroidism can cause:
    • Calcification in blood vessels and soft tissues: the high levels of phosphate cause it to stick to any available calcium, forming bone-like crystals.
  • Bone resorption:
    • Bone fractures
    • Osteoporosis
    • Osteopenia
  • Nephrolithiasis
  • Iatrogenic
    • Hypoparathyroidism
    • Recurrent laryngeal nerve damage
270
Q

Define Hypoparathyroidism

A

Hypoparathyroidism refers to a condition where there is an underproduction of parathyroid hormone.

271
Q

Aetiology of primary and secondary hypoparathyroidism

A
  • Autoimmune polyendocrine syndrome type 1: destroys parathyroid glands.
  • DiGeorge syndrome:*a deletion on the 22q11 part of the chromosome that causes a variety of immune and cardiac defects as well as parathyroid glands that can’t produce enough parathyroid hormone.
  • Autosomal-dominant hypoparathyroidism: a mutation in the parathyroid cell’s calcium-sensing receptor.

Secondary:

  • Removal of parathyroid gland during surgery
  • Hypomagnesium: magnesium is needed for PTH secretion
272
Q

Pathophysiology of Hypoparathyroidism

A

Low levels of parathyroid hormone lead to hypocalcaemia and hyperphosphatemia.

This makes neurons more excitable, which can trigger tetany.

Other symptoms include paresthesia - numbness or tingling of hands, feet, and around the mouth, changes in cardiac output, and calcification in places like the basal ganglia or the lens of the eye.

The spontaneous firing of neurons leads to Chvostek’s sign: facial muscles twitch after the facial nerve is lightly tapped.

It also can cause Trousseau’s sign: a blood pressure cuff occludes the brachial artery, and that pressure on the nerve is enough to make it fire, which results in a muscle spasm that makes the wrist and metacarpophalangeal joints flex.

273
Q

Signs of Hypoparathyroidism

A
  • Chvostek’s sign
  • Trousseau’s sign
  • Arrhythmias
274
Q

Symptoms of Hypoparathyroidism

A
  • Tetany
  • Paresthesia
  • Seizures
275
Q

Investigations for hypoparathyroidism

A
  • Bloods: low PTH, low calcium, low vitamin D, high phosphate.
  • Electrocardiogram: may show prolonged QT, prolonged ST segment, and arrhythmias e.g. torsade de pointes and atrial fibrillation.
276
Q

Differentials for hypoparathyroidism

A
  • Pseudohypoparathyroidism type 1A (Albright hereditary osteodystrophy): the kidneys and bones don’t respond to parathyroid hormone because of a defect in their parathyroid hormone receptor.Presents with: short metacarpals, round face, short stature, calcified basal ganglia. Low calcium, high phospate.
277
Q

Management for hypoparathyroidism

A
  • Calcium and vitamin D supplements
  • Recombinant human parathyroid hormone
278
Q

Complications of hypoparathyroidism

A

If the hypocalcaemia and hyperphosphatemia are severe, this can lead to life-threatening complications e.g. severe seizures and cardiac arrhythmias.

279
Q

Serotonin effects on the body

A
  • In the gastrointestinal tract, serotonin increases motility and peristalsis
  • In the vasculature, platelets take up the serotonin and later use it to constrict blood vessels, particularly after injury
  • In the connective tissue of the heart, it stimulates fibroblasts which make lots of collagen.
280
Q

Define Carcinoid tumour

A

Carcinoid tumour refers to a tumour of the neuroendocrine cells, resulting in excessive release of certain hormones.

281
Q

Carcinoid tumour vs carcinoid syndrome

A

Carcinoid tumour:

Neuroendocrine cells mutate and divide uncontrollably, leading to a carcinoid tumour. Most of the time this occurs in the gastrointestinal tract.

The cancerous neuroendocrine cells produce and secreting large amounts of hormones. Tumours can secrete:

Bradykinin, tachykinin, serotonin, substance P, VIP, gastrin, insulin, glucagon, ACTH, parathyroid and thyroid hormones.

Counterintuitively, they also express more somatostatin receptors on their surface.

Carcinoid tumours tend to be slow growing. Common primary sites include:

Appendix, small or large intestines, rectum, stomach, pancreas, liver, lungs, ovaries, testis, and the thymus.

Sometimes tumours can metastasise. A common site for this is the liver.

Carcinoid syndrome:

Associated with hepatic involvement.

Carcinoid syndrome occurs when there is a buildup of hormones produced by the neuroendocrine cells as the liver is no longer able to metabolise them.

  • Increased histamine and bradykinin: can cause vasodilation leading to flushing
  • Increased histamine: can cause itching
  • Increased serotonin: can cause thickening of fibrosis, particularly in the heart valves leading to heart dysfunction, like tricuspid regurgitation and pulmonary stenosis; and bronchoconstriction leading to asthma, shortness of breath, and wheezing.Also reduces the amount of tryptophan available to the body to make niacin, vitamin B3. Reduced levels of niacin can cause pellagra, a disease which causes symptoms like inflamed skin and mental confusion.
282
Q

Clinical manifestations of carcinoid tumour/syndrome

A
  • Diarrhoea
  • Shortness of breath
  • Flushing
  • Itching
  • Hepatic metastases: may cause RUQ pain

Symptoms are worsened by alcohol and stress: stimulate the neuroendocrine cells.

283
Q

Investigations for carcinoid tumour/syndrome

A
  • 24 hr urine 5-hydroxyindoleacetic acid:
    show increased levels
  • Chest X-ray/ chest or pelvis MRI/ CT: to identify location
  • Plasma chromogranin A: reflects tumour mass
  • Ostreoscan: injected radiolabelled somatostatin analogue, octreotide, to bind to the increased number of somatostatin receptors on tumour cells.
284
Q

Management for carcinoid tumour

A
  • Decreasing emotional stress and alcohol consumption
  • Somatostatin analogues: e.g. octreotide, inhibit hormone release
  • Surgical resection
  • Debulking embolisation or radiofrequency ablation of hepatic metastases can help with symptoms
285
Q

Complications of carcinoid tumours

A
  • GI tumours can cause: appendicitis, intussusception, or obstruction
  • Carcinoid crisis: tumour outgrow blood supply or is handled too much during surgery. This causes mediators to flood out causing life-threatening vasodilation, hypotension, tachycardia, bronchoconstriction and hyperglycaemia. Treated with high dose octreotide, supportive measurements and management of fluid balance.
286
Q

Prognosis for carcinoid tumours

A

5-8 years survival. 3 years if metastases present

80% of tumours metastasise!

287
Q

Define Phaeochromocytoma

A

Phaeochromocytoma is a rare tumour (usually benign) arising from chromaffin cells in the adrenal medulla resulting in the overproduction of catecholamines

Rule of 10s:

  • 10% extra-adrenal (paraganglioma): the most common extra-adrenal site is the organ of Zuckerkandl located at the bifurcation of the aorta.
  • 10% bilateral
  • 10% malignant
  • 10% familial
288
Q

Epidemiology of phaeochromocytoma

A
  • The typical presentation is between 30-50 years of age
  • Phaeochromocytomas are rare and account for only 0.05% of hypertensive individuals
289
Q

Risk factors for phaeochromocytoma

A
  • MEN 2A:phaeochromocytoma, medullary thyroid cancer, primary hyperparathyroidism
  • MEN 2B:phaeochromocytoma, medullary thyroid cancer, marfanoid habitus, mucosal neuromas
  • Von-Hippel-Lindau syndrome:phaeochromocytoma, renal cell carcinoma, cerebellar hemangioblastoma
  • Neurofibromatosis 1:phaeochromocytoma and skin changes, e.g. café-au lait spots and neurofibromas

Triggers include:

  • Stress
  • Physical exertion
  • Certain foods that contain tyramine
290
Q

Pathophysiology of phaeochromocytoma

A
  • Adrenaline is produced by the “chromaffin cells” in the adrenal medulla of the adrenal glands. A phaeochromocytoma is a tumour of the chromaffin cells that secretes unregulated and excessive amounts of catecholamines.
  • Adrenaline is a “catecholamine” hormone and neurotransmitter that stimulates the sympathetic nervous system and is responsible for the “fight or flight” response. In patients with a phaeochromocytoma the adrenaline tends to be secreted in bursts giving periods of worse symptoms followed by more settled periods.
  • Phaeochromocytoma’s typically form in one of the adrenal glands, but rarely can be in both and sometimes can even develop in other parts of the body where chromaffin cells are found like the carotid arteries in the neck, the bladder, and the abdominal aorta. If they arise from an extra-adrenal source, they are referred to as a paraganglioma.
  • In approximately 10% of cases, phaeochromocytoma is associated with familial conditions such as:
    • MEN 2: caused by a mutation in the RET gene, a protooncogene
    • Neurofibromatosis 1: caused by a mutation in the gene NF1 that encodes for a tumour suppressor protein called neurofibromin
    • Von-Hippel-Lindau disease: a mutation in the VHL gene which codes for the von Hippel-Lindau tumour suppressor protein.
291
Q

Signs of phaeochromocytoma

A
  • Hypertension: present in 90% of cases and usually refractory to treatment
  • Tachycardia
  • Paroxysmal atrial fibrillation
  • Hypertensive retinopathy
292
Q

Symptoms of phaeochromocytoma

A

Episodic headaches, palpitations, anxiety, sweating

293
Q

Primary investigations for phaeochromocytoma

A
  • 24 hr urinary metanephrine collection: metanephrine is a breakdown product of catecholamines, urinary and serum metanephrines are the first-line investigation; will both beelevated (97% sensitivity)
  • Plasma-free metanephrines
  • CT abdomen and pelvis: if there is biochemical evidence of a phaeochromocytoma, then CT imaging can be performed to look at the adrenals
294
Q

Other investigations for phaeochromocytoma

A
  • PET scan:used if metastatic disease is suspected and is generally preferred over scintigraphy
  • I-123 MIBG scintigraphy:radionucleotide incorporates itself into the phaeochromocytoma so helps localise metastatic tissue if suspected
  • Chromogranin A: may be used in combination with 24 hr urinary metanephrine collection for follow-up
295
Q

1st line management for Phaeochromocytoma

A
  • Peri-operative:initial alpha blockade (e.g. phenoxybenzamine)followed bybeta-blockade (e.g. propranolol)
    • Alpha-blockademust be offered for at least 7-14 days pre-operatively to allow for blood pressure and heart rate normalisation
    • Beta-blockadeis usually required for additional blood pressure control and management of tachyarrhythmias
    • Commencing a beta-blockerbeforean alpha-blocker can lead to unopposed alpha stimulation, subsequent vasoconstriction and a hypertensive crisis
  • Surgical:definitive management with laparoscopic adrenalectomy
296
Q

2nd line management for phaeochromocytoma

A

Medical: patients not suitable for surgery should be treated with long term anti-hypertensive agents

297
Q

Complications for phaeochromocytoma

A
  • Hypertensive crisis: patients can present with severe hypertension and evidence of end-organ damage e.g. cerebral haemorrhage, encephalopathy, arrhythmias, myocardial infarction, and renal failure. Requires IV anti-hypertensive therapy e.g. labetalol
  • Metastatic spread: commonly to lymph nodes, liver, bones, and lungs.
298
Q

Prognosis for phaeochromocytoma

A

Generally associated with an excellent prognosis.

Localised phaeochromocytomas have a 95% 5-year survival rate

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