The medical and surgical management of thyroid, pituitary and adrenal disorders Flashcards
Endocrine glands
Ductless glands that usually release a product into the bloodstream for transport to body targets
Endocrine gland examples
Adrenal glands (one at each kidney)
Pancreas (islets of Langerhands)
Parathyroid glands (on posterior surface of thyroid gland)
Thyroid gland
Endocrine system
Endocrine glands
Endocrine hormones
Endocrine targets: organs, tissues or cells
Endocrine hormones
Chemical signals produced by an endocrine gland that act at some distance from the gland
Endocrine targets
Targets are organs, tissues or cells capable of responding to the hormone due to the presence of a receptor that binds the hormone
Thyroid physiology
Largest of all endocrine glands
Produces hormones
-thyroxine (T4) and tri-iodothyronine (T3) regulate BMR
-calcitonin which has a role in regulating blood calcium levels
Unique among human endocrine glands - stores large amount of inactive hormone within extracellular follicles
Thyroid gland - surface anatomy
Clasps anterior and lateral surface of pharynx, larynx, oesophagus and trachea “like a shield”
Parathyroid glands usually lie between posterior border of thyroid gland and its sheath (usually 2 on each side of thyroid)
Internal jugular vein and common carotid artery lie postero-lateral to thyroid
The hypothalamo-pituitary-thyroid axis
Pituitary regulated by hypothalamus
Hypothalamus secretes thyrotoprin releasing hormone
Anterior pit. secretes TSH
Stimulates production of T3 and T4
Negative feedback: enough T3 and T4 will stop anterior pit/ hypothalamus producing TSH/ TRH
Measurement of thyroid hormones
Free thyroxine (T4) Free triiodothyronine (T3) Thyroid Stimulating Hormone (TSH)
Hypothyroidism
Autoimmune
Main problem within thyroid gland
Primary hypothyroidism: Low T4 –> body compensates and produces more TSH
-in mild cases body compensates and T4 will stay normal
Pituitary disease with thyroid hypofunction: low TSH –> low T4
Hypothyroidism - types
Primary failure of thyroid gland
Secondary to hypothalamic or pituitary failure
Dietary iodine deficiency
Hypothyroidism - Secondary to hypothalamic or pituitary failure
- hormone concentrations
- goitre
Lower T3 and T4
Lower TSH and / or lower TRH
No goitre
Hypothyroidism - dietary iodine deficiency
- hormone concentrations
- goitre
Lower T3 and T4
Higher TSH
Goitre - yes
Clinical features of hypothyroidism
Symptoms: weight gain lethargy increased sleep constipation cold intolerance dry skin hair loss menorrhagia deafness muscle weakness Signs: facial puffiness periorbital oedema bradycardia hoarseness delayed reflexes
Causes of hypothyroidism - primary
Dyshormonogenesis Iodine Deficiency Autoimmunity Post Radioactive Iodine Post Thyroidectomy Iodine Excess
Causes of hypothyroidism - primary
Dyshormonogenesis Iodine Deficiency Autoimmunity Post Radioactive Iodine Post Thyroidectomy Iodine Excess
Causes of secondary and tertiary hypothyroidism
Secondary: Pituitary Tumours Pituitary Granulomas Empty Sella Tertiary: Isolated TRH deficiency Hypothalamic disorders
Indications for screening for hypothyroidism
Congenital hypothyroidism Treatment of hyperthyroidism Neck Irradiation Pituitary Surgery or Irradiation Patients on lithium and amiodarone
Investigations and management
Thyroid function tests, Thyroid antibodies
Treat with levothyroxine
Dental complications in hypothyroidism
Delayed eruption Enamel hypoplasia Macroglossia Micrognathia Thick lips Dysgeusia
Hyperthyroidism types
Abnormal thyroidstimulating immunoglobulin (eg. Grave’s disease) Secondary to excess hypothalamic or pituitary secretion Hypersecreting thyroid tumour
Hyperthyroidism - Abnormal thyroidstimulating immunoglobulin
- hormone concentrations
- goitre
> T3 and T4
< TSH
Yes goitre
Hyperthyroidism - Secondary to excess hypothalamic or pituitary secretion -hormone concentrations -goitre
> T3 and T4
TSH and/ or > TRH
Yes goitre
Hyperthyroidism - Hypersecreting
thyroid tumour
-hormone concentrations
-goitre
> T3 and T4
< TSH
No goitre
Common causes of hyperthyroidism
Autoimmune thyroid disease o Graves Disease o Postpartum thyroiditis Toxic nodular goitre Toxic adenoma
Rare causes of hyperthyroidism
Amiodarone induced De Quervain’s thyroiditis Thyrotroph adenoma hCG hyperthyroidism ◦ Hydatidiform mole ◦ Choriocarcinoma
Hyperthyroidism
High T4
Suppressed TSH
Pituitary tumour (rare)
-increased TSH –> increased T4
Clinical features of hyperthyroidism
Symptoms: Weight loss Heat intolerance Anxiety, irritability Increased sweating Increased appetite Palpitations Loose bowels Signs: Goitre Tremor Warm moist skin Tachycardia Eye signs Thyroid bruit Muscle weakness Atrial fibrillation
Clinical features of Graves disease
Diffuse goitre Eye signs -exophthalmos (sclera showing on top) and proptosis Graves specific, and complain of dry eyes -lid lag and lid retraction general for hyperthyroidism Pretibial myxoedema -inflammation and redness on shins Vitiligo and features of other autoimmune disease -e.g. diabetes, Addisons FH of autoimmune thyroid disease
Investigations for Graves Disease
TSH receptor Antibodies (99% specific) TPO Antibodies Thyroglobulin Antibodies Thyroid Radioisotope scan (shows increased uptake)
Dental complications of hyperthyroidism
Accelerated dental eruption Maxillary or mandibular osteoporosis Increased susceptibility to caries Periodontal disease Increased sensitivity to epinephrine which may result in arrhythmias or palpitations Surgery, oral infection and stress may precipitate thyroid crises
Thyroid nodules - referral reason
New onset Increase in size Onset of pain Associated speech disturbance Lymphadenopathy Patient / Doctor concern
Joint thyroid clinic
Endocrinologist, Endocrine Surgeon
Primary Diagnostic tool – FNA ± US guided
Perform thyroid function tests prior to FNA to
exclude hyperthyroidism
Ultrasound and Radionuclide scans rarely
used
3 types of pituitary dysfunction
Tumour mass effects
Hormone excess
Hormone deficiency
Investigations of pituitary dysfunction
• Hormonal tests • If hormonal tests abnormal or tumour mass effects perform MRI pituitary
Local pituitary mass effects
Cranial nerve palsy and temporal lobe epilepsy
Visual field defects
CSF rhinorrhoea
Headaches
Pituitary hormone deficiency - GH
Short stature Abnormal body composition Reduced Muscle Mass Poor Quality of Life Rx: Growth Hormone
Pituitary hormone deficiency - LH/ FSH
Hypogonadism Reduced Sperm Count Infertility Menstruation Problems Rx: Testosterone in males; oestradiol ± progesterone in females
Pituitary hormone deficiency - TSH
Hypo Thyroidism
Rx: Levothyroxine
Pituitary hormone deficiency - ACTH
Adrenal failure
Pituitary hormone deficiency - ADH
Diabetes Insipidus (ADH deficiency - < water absorption in kidney resulting in polyuria & polydipsia) Rx: DDAVP
Causes of hypopituitarism
Pituitary tumours Radiotherapy Trauma Infarction Infiltration e.g. sarcoidosis, haemochromatosis Infection e.g. tuberculosis, syphilis Sheehan’s syndrome (post partum pituitary necrosis)
Acromegaly
• Excessive growth hormone secretion with
resultant high IGF-1 levels.
• Prevalence of 40-60 cases/million population.
• Incidence of 4 cases/million per year.
• Equal sex incidence
• Delayed diagnosis by 7 to 10 years
Acromegaly
- Excessive GH secretion with resultant high IGF-1 levels
- Prevalence of 40-60 cases/million pop
- Incidence of 4 cases/million/yr
- Equal sex incidence
- Delayed diagnosis by 7-10yrs
Clinical features of acromegaly
Head related: Coarse facial features Enlargement of supraorbital ridges Separation of teeth Prognathism Macroglossia Other Features: Headaches Spade-like hands Joint pains Excess sweating Hypertension Impaired glucose tolerance
Treatment for acromegaly and effectiveness
Surgical resection – TSS, TFS
- biochemical control
80% microadenomas
50% macroadenomas
Somatostatin analogues – 40% complete responders
Pegvisomant reduces IGF-1 to levels > 90%
Radiotherapy in unsuccessful surgery
Investigations for acromegaly
IGF1, dynamic tests, MRI pituitary
Dental related complications of acromegaly
Jaw Malocclusion Difficulty in speech due to macroglossia Teeth mobility Missing teeth Teeth separation Thickening of alveolar processes Enlarged posterior roots In 50% upper airways obstruction caused by pharyngeal hypertrophy and macroglossia with obstructive sleep apnoea
Involvement of ACTH and cortisol in hypothalamic-pituitary-adrenal axis
Hypothalamus produces corticotropinin producing hormone –> pituitary releases ACTH –> adrenal glands produce cortisol –> acts back on hypothalamus
Hypothalamus - pituitary - peripheral hormones
GnRH - LH, FSH - oestrogen/ androgen
Prolactin inhibiting factor (Dopamine) - PRL
GHRH/ Somatostatin (inhibits) - GH - Insulin like growth factor
Thyrotropin releasing hormone - TSH - T3 and T4
Corticotropin releasing hormone (CRH) - ACTH - cortisol
Vasopressin (ADH)
Oxytocin
Defining physiological cortisol circadian rhythm
Highest levels in morning? Lowest at night?
Cushing’s syndrome
Excess glucocorticoids due to
- pituitary tumor 70 - 80%
- adrenal tumor 10 - 20%
- ectopic ACTH tumor 10%
- iatrogenic
Clinical features of Cushing’s Syndrome
Weight gain 90% Menses probs 60% “Moon face” 75% Acne 40% HTN 75% Bruising 40% Striae 65% Osteopenia 40% Glucose intol. 65% Hyperpig 20% Muscle weak 60% K+ meta. alk. 15% Plethora 60% Hirsutism 65% Edema 40%
Investigations for Cushing’s syndrome
Hormonal tests:
-dynamic suppression tests (Dexamethasone
suppression tests) measuring cortisol, ACTH
Radiological (If hormonal tests are abnormal)
-MRI pituitary (pituitary tumour)
-CT adrenals (adrenal tumour)
-CT chest, abdomen, pelvis (ectopic ACTH tumour)
Cushing’s Syndrome Treatment
Surgery
Drugs
Consider radiotherapy for pituitary disease if surgery fails
Adrenal insufficiency
Lack of cortisol production
Addison’s Disease
The hypothtamlo-pitiutary-adrenal axis in primary and secondary adrenocortical insuffiency
Primary adrenocortical insufficiency: Less cortisol released from adrenal glands –> higher ACTH to compensate
-pigmentation as ACTH is released with melanin-stimulating hormone
Secondary adrenocortical insufficiency: Pituitary problem –> low ACTH –> Less cortisol released from adrenal glands
Causes of primary adrenal insufficiency
Autoimmune Tuberculosis Fungal infections Adrenal hemorrhage Congenital adrenal hypoplasia Sarcoidosis Amyloidosis Metastatic neoplasia
Causes of secondary adrenal insufficiency
After exogenous glucocorticoids After treatment of Cushing’s Hypothalamic or pituitary tumours
Clinical features of adrenal insufficiency
Weakness Skin and mucous membrane pigmentation Loss of weight, emaciation, anorexia, vomiting, diarrheoa Hypotension Salt craving Hypoglycemic episodes
Investigations for adrenal insufficiency
Hormonal tests: -dynamic stimulation tests (Synacthen test) measuring cortisol -ACTH, adrenal antibodies Radiological (If hormonal tests are abnormal) -MRI pituitary (pituitary disease) -CT or MRI adrenals (adrenal disease) -CXR if suspecting TB
Treatment for adrenal insufficiency
Hydrocortisone replacement treatment
Glucocorticoid cover for dental procedures
(STEROID COVER - DEPENDS ON PROCEDURE)
On treatment therapy e.g asthma, rheumatoid arthritis
◦ Prednisolone > 7.5mg
◦ Hydrocortisone > 30mg
◦ Dexamethasone > 0.75mg
On replacement therapy
◦ Addison’s e.g. Hydrocortisone 20/10mg
◦ ACTH deficiency 10/5/5mg
Simple Procedures: double dose one hour before surgery,
double dose oral medication for 24 hours
Major Procedures/ GA: hydrocortisone 100mg im at
induction and double dose oral medication for 24 hours
Surgery and other endocrine disorders
• Hyperthyroidism – render euthyroid • Phaeochromocytoma – treat before any surgery • Cushing’s – avoid infections and pathological fractures; steroid cover • Refer to endocrinologist
Endocrine causes of hypertension
- Primary aldosteronism
- Phaeochromocytoma
- Acromegaly
- Cushing’s syndrome
- Hypothyroidism
- Hyperthyroidism
Role of calcium
Average person has 1kg of calcium 99% in the skeleton Ionised calcium in ECF <1% –cofactor in coagulation –skeletal mineralisation –membrane stabilisation (neuronal conduction)
Calcium homeostasis response to a decrease in serum calcium
- -> increased PTH
1. > bone resorption
2. > Ca2+ absorption in gut
3. > Ca2+ reabsorption in kidneys
Parathyroid hormone actions
Kidney: - > Ca2+ reabsorption - < phosphate reabsorption - > 1 alpha - hydroxylation of 25-OH vit D Bone: -> bone remodelling -bone resorption > bone formation No direct effect on gut - > Ca2+ absorption because increased 1,25 (OH)2 vit D
Calcium homeostasis is an example of
Negative feedback
-return serum ionised calcium back to the set point of about 1.1
mmol/l
Relationship between serum calcium and PTH
Small changes in serum calcium result in big changes in PTH
Inverse relationship
-low Ca –> high PTH
-high Ca –> low PTH
Abnormalities in PTH
May be appropriate
–to maintain calcium balance
May be inappropriate
–cause calcium imbalance
Is it really hypocalcaemia?
Low serum albumin –> low total serum calcium: but not a low ionised calcium
Corrected calcium = total serum calcium + 0.02 * (40 – serum albumin)
Serum calcium = 2.08 mmol/L
Serum albumin = 30 g/L
Corrected calcium = 2.28 mmol/L
Causes of hypocalcaemia
Vitamin D deficiency/ Osteomalacia Hypoparathyroidism –post surgery, radiation, autoimmune disease –Hereditary (Autosomal dominant hypocalcaemia) –syndromes (Di George, HDR [hypopara, deafness, renal dysplasia] etc) –infiltration (Wilson’s disease, haemochromatosis) Chronic renal failure Magnesium deficiency Pseudohypoparathyroidism Acute pancreatitis Multiple citrated blood transfusions
Consequences of hypocalcaemia
Parasthesia Muscle spasm –hands and feet –larynx –premature labour Seizures Basal ganglia calcification Cataracts Dental hypoplasia ECG abnormalities –long QT interval (can predispose to ventricular arrhythmias) *Chvostek's sign *Trousseau's sign*
Adrenal crisis
a constellation of symptoms that indicate severe adrenal insufficiency caused by insufficient levels of the hormone cortisol
- potentially life threatening
- requires immediate emergency treatment
Chvostek’s sign
tap over facial nerve and look for spasm of facial muscles
Trousseau’s sign
Inflate the BP cuff to 20mm Hg above systolic for 5 minutes
Looking for clues for hypocalcaemia
• History of neck surgery • Presence of other autoimmune conditions • History of congenital defects and immunodeficiency • Family history to suggest genetic cause • Drug history e.g antiepileptics • Neck scar, candidiasis, vitiligo, generalized bronzing • Growth failure, hearing loss
Vitamin D deficiency (secondary hyperparathyroidism)
Low calcium
Increased PTH
Low phosphate
Appropriate PTH
Hypoparathyroidism
Decreased PTH (inappropriate)
- < renal calcium reabsorption –> > relative calcium excretion
- > renal phosphate reabsorption –> increased serum phosphate
- < bone resorption
- < formation of 1,25(OH)2D –> decreased intestinal calcium absorption
- —–> Decreased serum calcium
Pseudohypoparathyroidism
• Resistance to parathyroid hormone
–type 1 – mutation with deficient Gα
subunit
–1a Albright hereditary osteodystrophy
Pseudohypoparathyroidism - symptoms
- Short stature
- Obesity
- Round facies
- Mild learning difficulties
- Subcutaneous ossification
- Short fourth metacarpals
- Other hormone resistance
Pseudohypoparathyroidism hormones
Low calcium
> PTH
> phosphate
Appropriate PTH?
Management of hypocalcaemia
Mild (asymptomatic, >1.9mmol/L)
-commence oral calcium supplements (AdCal 3 tabs bd)
-post-thyroidectomy - calcium supplements and consider adding 1-alphacalcidol (0.25mcg/day)
-if vit D deficiency, load with cholecalciferol for 12 weeks
-if hypomagnesaemia, replace magnesium
Severe (symptomatic, <1.9mmol/L)
-10-20mls of 10% calcium gluconate over 10 mins (in 50-100mls of 5% dextrose)
-dilute 100mls of 10% calcium gluconate in 1L of normal saline (at 50-100mls/hr)
-post-op hypocalcaemia o r hypoparathyroidism give 1-alphacalcidol 0.25mcg/day
Monitor adjusted calcium levels closely
LISTEN TO SLIDE
Is it really hypercalcaemia?
- Tourniquet on for too long
- Sample old and haemolysed
- ? Recheck
Causes of hypercalcaemia
• Malignancy – bone mets, myeloma, PTHrP, lymphoma • Primary hyperparathyroidism -first two together make up 90% • Thiazides • Thyrotoxocosis • Sarcoidosis • Familial hypocalciuric / benign hypercalcaemia • Immobilisation • Milk-alkali • Adrenal insufficiency • Phaeochromocytoma
Hypercalcaemia symptoms
• Thirst, polyuria • Nausea • Constipation • Confusion coma
Hypercalcaemia conequences (complications) of symptoms
• Pancreatitis • Gastric ulcer • Renal stones • ECG abnormalities -Short QT
Signs of hypercalcaemia
• Confusion, hypotonia, hyporeflexic • Dehydration • Signs of malignancy (enlarged liver, clubbing, thyroid mass, breast lump, lymph nodes) • Faecal impaction • Irregular pulse (arrhythmia,
Approach to hypercalcaemia
• Identify any drugs that may cause hypercalcaemia
(thiazides, lithium, Vitamin D)
• Identify whether presence of renal failure ? Tertiary hyperparathyroidism
• Check serum PTH and if high or normal perform 24-hour urine calcium
excretion (Urine Calcium/Urine Creatinine x Plasma Creatinine)
• If PTH high or normal and urine calcium excretion > 0.01 mmol/l – Primary
Hyperparathyroidism
• If PTH high or normal and urine calcium excretion < 0.01 mmol/l – FHH
• If PTH low or suppressed – exclude malignancy,
hyperthyroidism, Addison’s, sarcoidosis, granulomatous
disorders
Hypercalcaemia of malignancy - hormones
High serum calcium –> low PTH (appropriate?**)
- Decreased bone resorption
- Decreased calcium absorption from gut
- Decreased calcium reabsorption from kidney
- phosphate not affected?
Hypercalcaemia of malignancy
• About 20 to 30% of patients with cancer
• 80% are due to bony metastases (breast, thyroid , kidney,
lung, prostate)
• 20% due to PTHrP release (others secrete Vitamin D,
ectopic PTH)
• Osteoclastic Hypercalcaemia
Primary hyperparathyroidism causes
80% due to single benign adenoma
15-20% due to four gland hyperplasia
-may be part of MEN I or II
<0.5% malignant
Consequences of primary hyperparathyroidism
• Bones – Osteitis fibrosa cystica – Osteoporosis • Kidney stones • Psychic groans – confusion • Abdominal moans – Constipation – Acute pancreatitis
Primary hyperparathyroidism - hormones
Increased bone resorption –> hypercalcaemia
Increased renal reabsorption of calcium –> hypercalcaemia
Increased calcium absorption –> hypercalcaemia
-high PTH
-low phosphate
-inappropriate PTH
Management of primary hyperparathyroidism
Indications for surgery
• Serum calcium > 0.25 mmol/l from upper limit
• Creatinine clearance < 60 ml/min
• T-score < -2.5 at any site and/or previous fragility
fracture at spine, hip, radius, femoral neck
• 24 hour urine calcium >400mg/day (>10mmol/day)
• Nephrocalcinosis or nephrolithiasis
• < 50 years
Tertiary hyperparathyroidism
Renal failure –> vit D deficiency –> decreased calcium absorption –> decreased serum calcium
- > PTH
- < serum phosphate
- impaired mineralisation
- high alkaline phosphatase
- -> nodular hyperplasia and autonomy
Management of hypercalcaemia
• Intravenous fluids Normal 0.9% saline
• Loop diuretic if risk of overload ONLY
• Intravenous bisphosphonates e.g
pamidronate,
zoledronic acid (make sure PTH sample taken)
• Corticosteroids e.g Vitamin D intoxication,
sarcoidosis
Treatment of Graves
Medical
-drug side effects e.g.nausea, vomiting, leucopenia leading to agranulocytosis, aplastic anaemia, drug fever, cholestatic jaundice
Surgical
Radioactive iodine
