The medical and surgical management of thyroid, pituitary and adrenal disorders

Question 1

Endocrine glands

Answer 1

Ductless glands that usually release a product into the bloodstream for transport to body targets

Question 2

Endocrine gland examples

Answer 2

Adrenal glands (one at each kidney)
Pancreas (islets of Langerhands)
Parathyroid glands (on posterior surface of thyroid gland)
Thyroid gland

Question 3

Endocrine system

Answer 3

Endocrine glands
Endocrine hormones
Endocrine targets: organs, tissues or cells

Question 4

Endocrine hormones

Answer 4

Chemical signals produced by an endocrine gland that act at some distance from the gland

Question 5

Endocrine targets

Answer 5

Targets are organs, tissues or cells capable of responding to the hormone due to the presence of a receptor that binds the hormone

Question 6

Thyroid physiology

Answer 6

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

Question 7

Thyroid gland - surface anatomy

Answer 7

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

Question 8

The hypothalamo-pituitary-thyroid axis

Answer 8

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

Question 9

Measurement of thyroid hormones

Answer 9

Free thyroxine (T4)
Free triiodothyronine (T3)
Thyroid Stimulating Hormone (TSH)

Question 10

Hypothyroidism

Answer 10

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

Question 11

Hypothyroidism - types

Answer 11

Primary failure of thyroid gland
Secondary to hypothalamic or pituitary failure
Dietary iodine deficiency

Question 12

Hypothyroidism - Secondary to hypothalamic or pituitary failure

• hormone concentrations
• goitre

Answer 12

Lower T3 and T4
Lower TSH and / or lower TRH
No goitre

Question 13

Hypothyroidism - dietary iodine deficiency

• hormone concentrations
• goitre

Answer 13

Lower T3 and T4
Higher TSH
Goitre - yes

Question 14

Clinical features of hypothyroidism

Answer 14

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

Question 15

Causes of hypothyroidism - primary

Answer 15

 Dyshormonogenesis
 Iodine Deficiency
 Autoimmunity
 Post Radioactive Iodine
 Post Thyroidectomy
 Iodine Excess

Question 16

Causes of hypothyroidism - primary

Answer 16

 Dyshormonogenesis
 Iodine Deficiency
 Autoimmunity
 Post Radioactive Iodine
 Post Thyroidectomy
 Iodine Excess

Question 17

Causes of secondary and tertiary hypothyroidism

Answer 17

Secondary:
 Pituitary Tumours
 Pituitary Granulomas
 Empty Sella
Tertiary:
 Isolated TRH deficiency
 Hypothalamic disorders

Question 18

Indications for screening for hypothyroidism

Answer 18

 Congenital hypothyroidism
 Treatment of hyperthyroidism
 Neck Irradiation
 Pituitary Surgery or Irradiation
 Patients on lithium and amiodarone

Question 19

Investigations and management

Answer 19

 Thyroid function tests, Thyroid antibodies

 Treat with levothyroxine

Question 20

Dental complications in hypothyroidism

Answer 20

 Delayed eruption
 Enamel hypoplasia
 Macroglossia
 Micrognathia
 Thick lips
 Dysgeusia

Question 21

Hyperthyroidism types

Answer 21

Abnormal thyroidstimulating immunoglobulin
(eg. Grave’s
disease)
Secondary to excess
hypothalamic or
pituitary secretion
Hypersecreting
thyroid tumour

Question 22

Hyperthyroidism - Abnormal thyroidstimulating immunoglobulin

• hormone concentrations
• goitre

Answer 22

> T3 and T4
< TSH
Yes goitre

Question 23

Hyperthyroidism - Secondary to excess
hypothalamic or
pituitary secretion
-hormone concentrations
-goitre

Answer 23

> T3 and T4
TSH and/ or > TRH
Yes goitre

Question 24

Hyperthyroidism - Hypersecreting
thyroid tumour
-hormone concentrations
-goitre

Answer 24

> T3 and T4
< TSH
No goitre

Question 25

Common causes of hyperthyroidism

Answer 25

```  Autoimmune thyroid disease o Graves Disease o Postpartum thyroiditis  Toxic nodular goitre  Toxic adenoma ```

Question 26

Rare causes of hyperthyroidism

Answer 26

```  Amiodarone induced  De Quervain’s thyroiditis  Thyrotroph adenoma  hCG hyperthyroidism ◦ Hydatidiform mole ◦ Choriocarcinoma ```

Question 27

Hyperthyroidism

Answer 27

High T4 Suppressed TSH Pituitary tumour (rare) -increased TSH --> increased T4

Question 28

Clinical features of hyperthyroidism

Answer 28

``` 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 ```

Question 29

Clinical features of Graves disease

Answer 29

```  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 ```

Question 30

Investigations for Graves Disease

Answer 30

```  TSH receptor Antibodies (99% specific)  TPO Antibodies  Thyroglobulin Antibodies  Thyroid Radioisotope scan (shows increased uptake) ```

Question 31

Dental complications of hyperthyroidism

Answer 31

```  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 ```

Question 32

Thyroid nodules - referral reason

Answer 32

```  New onset  Increase in size  Onset of pain  Associated speech disturbance  Lymphadenopathy  Patient / Doctor concern ```

Question 33

Joint thyroid clinic

Answer 33

 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

Question 34

3 types of pituitary dysfunction

Answer 34

Tumour mass effects Hormone excess Hormone deficiency

Question 35

Investigations of pituitary dysfunction

Answer 35

``` • Hormonal tests • If hormonal tests abnormal or tumour mass effects perform MRI pituitary ```

Question 36

Local pituitary mass effects

Answer 36

Cranial nerve palsy and temporal lobe epilepsy Visual field defects CSF rhinorrhoea Headaches

Question 37

Pituitary hormone deficiency - GH

Answer 37

``` Short stature Abnormal body composition Reduced Muscle Mass Poor Quality of Life Rx: Growth Hormone ```

Question 38

Pituitary hormone deficiency - LH/ FSH

Answer 38

``` Hypogonadism Reduced Sperm Count Infertility Menstruation Problems Rx: Testosterone in males; oestradiol ± progesterone in females ```

Question 39

Pituitary hormone deficiency - TSH

Answer 39

Hypo Thyroidism | Rx: Levothyroxine

Question 40

Pituitary hormone deficiency - ACTH

Answer 40

Adrenal failure

Question 41

Pituitary hormone deficiency - ADH

Answer 41

``` Diabetes Insipidus (ADH deficiency - < water absorption in kidney resulting in polyuria & polydipsia) Rx: DDAVP ```

Question 42

Causes of hypopituitarism

Answer 42

```  Pituitary tumours  Radiotherapy  Trauma  Infarction  Infiltration e.g. sarcoidosis, haemochromatosis  Infection e.g. tuberculosis, syphilis  Sheehan’s syndrome (post partum pituitary necrosis) ```

Question 43

Acromegaly

Answer 43

• 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

Question 44

Acromegaly

Answer 44

* 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

Question 45

Clinical features of acromegaly

Answer 45

``` 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 ```

Question 46

Treatment for acromegaly and effectiveness

Answer 46

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

Question 47

Investigations for acromegaly

Answer 47

IGF1, dynamic tests, MRI pituitary

Question 48

Dental related complications of acromegaly

Answer 48

```  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 ```

Question 49

Involvement of ACTH and cortisol in hypothalamic-pituitary-adrenal axis

Answer 49

Hypothalamus produces corticotropinin producing hormone --> pituitary releases ACTH --> adrenal glands produce cortisol --> acts back on hypothalamus

Question 50

Hypothalamus - pituitary - peripheral hormones

Answer 50

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

Question 51

Defining physiological cortisol circadian rhythm

Answer 51

Highest levels in morning? Lowest at night?

Question 52

Cushing's syndrome

Answer 52

Excess glucocorticoids due to - pituitary tumor 70 - 80% - adrenal tumor 10 - 20% - ectopic ACTH tumor 10% - iatrogenic

Question 53

Clinical features of Cushing's Syndrome

Answer 53

``` 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% ```

Question 54

Investigations for Cushing's syndrome

Answer 54

 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)

Question 55

Cushing's Syndrome Treatment

Answer 55

 Surgery  Drugs  Consider radiotherapy for pituitary disease if surgery fails

Question 56

Adrenal insufficiency

Answer 56

Lack of cortisol production | Addison's Disease

Question 57

The hypothtamlo-pitiutary-adrenal axis in primary and secondary adrenocortical insuffiency

Answer 57

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

Question 58

Causes of primary adrenal insufficiency

Answer 58

```  Autoimmune  Tuberculosis  Fungal infections  Adrenal hemorrhage  Congenital adrenal hypoplasia  Sarcoidosis  Amyloidosis  Metastatic neoplasia ```

Question 59

Causes of secondary adrenal insufficiency

Answer 59

```  After exogenous glucocorticoids  After treatment of Cushing’s  Hypothalamic or pituitary tumours ```

Question 60

Clinical features of adrenal insufficiency

Answer 60

``` Weakness Skin and mucous membrane pigmentation Loss of weight, emaciation, anorexia, vomiting, diarrheoa Hypotension Salt craving Hypoglycemic episodes ```

Question 61

Investigations for adrenal insufficiency

Answer 61

```  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 ```

Question 62

Treatment for adrenal insufficiency

Answer 62

Hydrocortisone replacement treatment

Question 63

Glucocorticoid cover for dental procedures

Answer 63

(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

Question 64

Surgery and other endocrine disorders

Answer 64

``` • Hyperthyroidism – render euthyroid • Phaeochromocytoma – treat before any surgery • Cushing’s – avoid infections and pathological fractures; steroid cover • Refer to endocrinologist ```

Question 65

Endocrine causes of hypertension

Answer 65

* Primary aldosteronism * Phaeochromocytoma * Acromegaly * Cushing’s syndrome * Hypothyroidism * Hyperthyroidism

Question 66

Role of calcium

Answer 66

``` Average person has 1kg of calcium 99% in the skeleton Ionised calcium in ECF <1% –cofactor in coagulation –skeletal mineralisation –membrane stabilisation (neuronal conduction) ```

Question 67

Calcium homeostasis response to a decrease in serum calcium

Answer 67

- -> increased PTH 1. > bone resorption 2. > Ca2+ absorption in gut 3. > Ca2+ reabsorption in kidneys

Question 68

Parathyroid hormone actions

Answer 68

``` 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 ```

Question 69

Calcium homeostasis is an example of

Answer 69

Negative feedback -return serum ionised calcium back to the set point of about 1.1 mmol/l

Question 70

Relationship between serum calcium and PTH

Answer 70

Small changes in serum calcium result in big changes in PTH Inverse relationship -low Ca --> high PTH -high Ca --> low PTH

Question 71

Abnormalities in PTH

Answer 71

May be appropriate –to maintain calcium balance May be inappropriate –cause calcium imbalance

Question 72

Is it really hypocalcaemia?

Answer 72

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

Question 73

Causes of hypocalcaemia

Answer 73

``` 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 ```

Question 74

Consequences of hypocalcaemia

Answer 74

``` 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* ```

Question 75

Adrenal crisis

Answer 75

a constellation of symptoms that indicate severe adrenal insufficiency caused by insufficient levels of the hormone cortisol - potentially life threatening - requires immediate emergency treatment

Question 76

Chvostek's sign

Answer 76

tap over facial nerve and look for spasm of facial muscles

Question 77

Trousseau's sign

Answer 77

Inflate the BP cuff to 20mm Hg above systolic for 5 minutes

Question 78

Looking for clues for hypocalcaemia

Answer 78

``` • 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 ```

Question 79

Vitamin D deficiency (secondary hyperparathyroidism)

Answer 79

Low calcium Increased PTH Low phosphate Appropriate PTH

Question 80

Hypoparathyroidism

Answer 80

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

Question 81

Pseudohypoparathyroidism

Answer 81

• Resistance to parathyroid hormone –type 1 – mutation with deficient Gα subunit –1a Albright hereditary osteodystrophy

Question 82

Pseudohypoparathyroidism - symptoms

Answer 82

* Short stature * Obesity * Round facies * Mild learning difficulties * Subcutaneous ossification * Short fourth metacarpals * Other hormone resistance

Question 83

Pseudohypoparathyroidism hormones

Answer 83

Low calcium > PTH > phosphate Appropriate PTH?

Question 84

Management of hypocalcaemia

Answer 84

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*

Question 85

Is it really hypercalcaemia?

Answer 85

* Tourniquet on for too long * Sample old and haemolysed * ? Recheck

Question 86

Causes of hypercalcaemia

Answer 86

``` • 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 ```

Question 87

Hypercalcaemia symptoms

Answer 87

``` • Thirst, polyuria • Nausea • Constipation • Confusion coma ```

Question 88

Hypercalcaemia conequences (complications) of symptoms

Answer 88

``` • Pancreatitis • Gastric ulcer • Renal stones • ECG abnormalities -Short QT ```

Question 89

Signs of hypercalcaemia

Answer 89

``` • Confusion, hypotonia, hyporeflexic • Dehydration • Signs of malignancy (enlarged liver, clubbing, thyroid mass, breast lump, lymph nodes) • Faecal impaction • Irregular pulse (arrhythmia, ```

Question 90

Approach to hypercalcaemia

Answer 90

• 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

Question 91

Hypercalcaemia of malignancy - hormones

Answer 91

High serum calcium --> low PTH (appropriate?**) 1. Decreased bone resorption 2. Decreased calcium absorption from gut 3. Decreased calcium reabsorption from kidney - phosphate not affected?

Question 92

Hypercalcaemia of malignancy

Answer 92

• 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

Question 93

Primary hyperparathyroidism causes

Answer 93

80% due to single benign adenoma 15-20% due to four gland hyperplasia -may be part of MEN I or II <0.5% malignant

Question 94

Consequences of primary hyperparathyroidism

Answer 94

``` • Bones – Osteitis fibrosa cystica – Osteoporosis • Kidney stones • Psychic groans – confusion • Abdominal moans – Constipation – Acute pancreatitis ```

Question 95

Primary hyperparathyroidism - hormones

Answer 95

Increased bone resorption --> hypercalcaemia Increased renal reabsorption of calcium --> hypercalcaemia Increased calcium absorption --> hypercalcaemia -high PTH -low phosphate -inappropriate PTH

Question 96

Management of primary hyperparathyroidism

Answer 96

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

Question 97

Tertiary hyperparathyroidism

Answer 97

Renal failure --> vit D deficiency --> decreased calcium absorption --> decreased serum calcium - > PTH - < serum phosphate - impaired mineralisation - high alkaline phosphatase - -> nodular hyperplasia and autonomy

Question 98

Management of hypercalcaemia

Answer 98

• 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

Question 99

Treatment of Graves

Answer 99

Medical -drug side effects e.g.nausea, vomiting, leucopenia leading to agranulocytosis, aplastic anaemia, drug fever, cholestatic jaundice Surgical Radioactive iodine