Endocrine Disorders

Disorders of thyroid gland: thyrotoxicosis/hyperthyroidism, hypothyroidism, thyroid enlargement

(goitre/thyroid nodules).
1. Hypothyroidism
P° - disease of thyroid gland. S° - pituitary/hypothalamic lesion.
Clinical features:
Tiredness, somnolence, weight gain, cold intolerance, bradycardia, anemia, constipation, hyperlipidemia,
hoarseness, goitre, hypertension, angina, aches and pains, muscle stiffness, dry flaky skin, alopecia,
myalgia, impotence, myxoedema.
Investigations:
• Thyroid function tests (low T4, T3 is not determined because does not differentiate btw
euthyroid/hypothyroid patients, TSH high in P° and low in S°, antithyroid peroxidase and
antithyroglobulin antibodies high in Hashimotos thyroiditis).
• Serum lactate dehydrogenase and creatine kinase high.
• Serum cholesterol and triglyceride high.
• Serum sodium low.
• Anemia (with normal or raised MCV)
• ECG (Sinus bradycardia with low voltage complexes).
Complications: coronary artery disease, infections, myxoedema madness/coma, infertility, pregnancy results in
miscarriage or baby with low IQ.
Management:
Replacement therapy – Thyroxine (taken in morning, single dose. Correct dose restores TSH to normal.
Half life 7 days.)
• 50 ug/day for first 3 weeks.
• 100 ug/day for next 3 weeks.
• 150 ug/day for whole life.
For patients with heart disease: 25ug/day with b blockers and vasodilator. Patients with age over 60: 25
ug/day.
Patient feels better within 2-3 weeks. Patients with IHD – don’t tolerate therapy, need angioplasty.
Pregnancy - 50ug more thyroxine than normally given.
Myxoedema Coma: hypothermia, hypoglycemia, hyponatremia, confusion/coma. T3 2.5-5ug IV or orally 8
hourly, then via tablet. Oxygen, hydrocortisone 100 mg IV 8 hourly, 5% dextrose water, antibiotics. Rewarming
of blanket.

2. Hyperthyroidism (Thyrotoxicosis)
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Causes: Graves disease, multinodular goitre, thyroiditis, autonomously functioning thyroid nodules (toxic
adenoma).
Clinical features:
Weight loss, normal or increased appetite, heat intolerance, tachycardia, palpitations, tremor, irritability,
lid lag, lid retraction, ophthalmopathy (periorbital edema, conjunctival irritation, exophthalmos,
diplopia), diarrhoea, increased sweating, excessive lacrimation, muscle weakness, thirst, osteoporosis.
Investigations:
• Thyroid function tests (low TSH, T3 T4 and free thyroxin all high, TSH receptor antibody high in
Graves, antithyroglobulin/antimicrosomal antibodies high, serum ANA, anti DNA high)
• Thyroid Radionuclide scan (inc in Graves and toxic nodular goitre, dec in subacute thyroiditis)
• MRI of orbits (ophthalmopathy)
• Hypercalcemia
• Alkaline phosphatase high
• Anemia (low granulocytes)
• Raised ESR
Management:
• Antithyroid drugs – Carbimazole (0-3 weeks 40-60mg daily, 4-8 weeks 20-40mg daily,
maintenance dose 5-20mg daily. Duration: 18-24 months. Divided doses. OR full dose 40mg given
to suppress thyroid completely and 100ug thyroxine until euthyroid state reached. Duration: 18
months.). Propylthiouracil (safe in pregnancy). Meanwhile b blockers given. Left when patient
becomes euthyroid.
• Radioactive iodine.
• Surgery (if recurrence, poor drug compliance, large goitre. Patient must be euthyroid. Drugs
stopped 2 weeks prior. Potassium iodide 600mg TDS given instead).
Drugs in less than 40y/o patient. If relapse occurs, then surgery. In above 40 y/o, radioactive iodine, also
if recurrence after surgery occurs.
Thyroid crises: hyperpyrexia, tachycardia, vomiting, diarrhoea, dehydration, restlessness.

3. Hyperparathyroidism
(Principle of parathyroid gland: parathyroid gland secretes PTH that increases Ca levels)
• P° - parathyroid adenoma.
• S° - as result of low serum calcium levels in chronic Renal failure, malabsorption, rickets, osteomalacia.
• T° - parathyroid tumor (prolonged S° hyperparathyroidism).
Usually occurs in women above 50. Otherwise it’s multiple endocrine neoplasia.
Clinical features:
Hypercalcemia, hypercalciuria, nephrocalcinosis, renal Stones, bone resorption – fractures or cystic
disease. Bone pain, swelling, hypercalcemia (anorexia, nausea, constipation, muscular weakness, weight

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loss, anemia, pruritus, hypertension, calciphylaxis. (Renal) polydipsia, polyuria, hematuria, renal colic,
nephritis. (Bone) – decalcification, fibrosis – Bone pain, tenderness, fracture, deformity, falling of teeth,
loss of cortical Bone, gain of trabecular, osteitis fibrosa cystica(brown tumor). (GIT) peptic ulceration,
pancreatitis. (CNS) fatigue, paresthesia.
Investigations:
• Serum Ca (normal is 9-11mg, in this: >11)
• Serum PTH high.
• Alkaline phosphatase high.
• Serum phosphate low.
• Urine Ca excretion high.
• Tc 99m sestamibi scan (to localize adenoma).
• Neck ultrasound/MRI.
• Xrays (cortical erosion in phalanges, salt and pepper appearance on lateral xrays of skull,
articular cartilage calcification).
Treatment:
Surgical removal of adenoma. Medical – large fluid intake. Bisphophonates (inhibit bone resorption).
Pamidronate, zoldetronate, alandronate.
Hypercalcemic crises: hypercalcemia, vomiting, fever, dehydration, hypotension, altered consciousness,
abdominal pain. Treatment – fluid replacement with normal saline 4-6l, bisphosphonates, rapid therapy(forced
diuretics with saline and furosemide, glucocorticoids, calcitonin, hemolysis, treat the cause.

4. Hypoparathyroidism
Causes: damage to glands after thyroid surgery, idiopathic, pseudo (tissue resistance to hormones) high PTH,
skeletal abnormalities.
(Causes of hypocalcemia: bisphonates, calcitonin, high phosphate, vitamin D deficiency/resistance, acute
pancreatitis, hypoparathyroidism).
Clinical features:
Tetany (in severe cases), hypocalcemia, paresthesia, numbness around mouth, cramps, anxiety, followed
by convulsions, dystonia, psychosis. Signs: trousseus sign, chvosteks sign).
Treatment:
Parathyroid hormones preparations are unstable, vitamin D preparation, acute phase calcium IV.
Tetany – excitability of peripheral nerves due to low calcium or alkalosis. Calcium is normal in body but less in
ionised form.
Clinical features:
Triad in children – carpopedal spasm, stridor, convulsion. (Metacarpophalangeal joints are flexed,
interphalangeal joints of fingers and thumb extended and there is apposition of thumb. Stridor is due to
spasm of glottis.) Adults – tingling in hands, feet, around mouth. Latent tetany – trousseus sign (inflation
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of syphgmomanometer cuff on upper arm to more than systolic pressure followed by carpal spasm within
3 minutes), chvosteks sign (gentle tapping over facial nerve causes twitching of facial muscles).
Treatment:
Injection calcium gluconate 10ml IV slowly then 10-40ml of 10% calcium gluconate in litre of normal
saline over 4-8 hours. If not relieved, then Mg is given. Correction of alkalosis: IV saline in persistent
vomiting. Ammonium chloride 2g orally. Rebreathing in paper bag. Chronic – vitamin D in form of
alfacalcidol 0.5-3ug daily.

5. Pheochromocytomas
Rare tumors (90% from adrenal medulla, 10% malignant). Secretes catecholamines and is responsible for
hypertension.
Clinical features:
Excess catecholamines secretion, anxiety, palpitations, Tremors, sweating, headache, flushing, nausea,
weight loss, raynaud phenomenon (finger discoloration due to temperature change), chest pain, polyuria,
hypertension, tachycardia, arrhythmia, orthostatic hypotension, pallor, glycosuria, fever.
Investigations:
• 24 hour urinary vallinylmandelic acid (VMA)
• Metanephrine/normetanephrine (screening test).
• CT scan of abdomen (to localize tumors).
• Scanning (for extra adrenal tumors).
Treatment:
Medical – prep for surgery; a blockers – phenoxybenzamine 10-20mg 3-4 times daily. If tachycardia
occurs – then b blockers (propranolol). Surgical – tumor removed. Prep with 6 weeks course of b
blockers.

6. Multiple Endocrine Neoplasia (MEN 1& MEN 2)

Tumors in a lot of endocrine glands.
• MEN 1 (werner's syndrome) – P° hyperparathyroidism, functioning pituitary tumors, pancreatic tumors
(insulinoma, gastrinoma).
• MEN 2(sipple's syndrome) – P° hyperparathyroidism, medullary carcinoma of thyroid,
pheochromocytoma.

7. Craniopharyngioma
Benign tumors in sella turcica (often cystic). Compress surrounding structures like hypothalamus (hyperphagia,
obesity, loss of sensation of thirst, disturbed temperature regulation). Transsphenoidal surgery, craniotomy
(with complications of hypothalamus), radiotherapy.
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 8. Amenorrhea
Failure of menstruation. Primary and secondary.
P° - women never menstruated regardless of presence of S° sexual characteristics. Congenital defects of uterus,
cervix, vagina, ovarian failure.
S° - cessation of menstruation.
Investigations: Serum FSH, LH, prolactin, estradiol, TSH.
Treatment: of cause.

9. Hirsutism
Excessive hair growth in androgen dependent distribution in women (upper lip, chin, chest, back, lower
abdomen, thigh, forearm). Androgen secreting tumor – high androgen – frontal balding, muscularity,
clitromegaly, deepening of voice.
Investigations: Serum testosterone, FSH, LH, prolactin normal.

10. Gynaecomastia
Presence of breast glandular tissue in men. Imbalance btw estrogen and androgen (estrogen promotes and
androgen opposes).
Causes: idiopathic, physiological (neonates, peripubertal, old age), drug induced (spironolactone, digoxin,
cimetidine, antiandrogen), hypogonadism (P° - klinefelter, mumps, orchids, TB, chemotherapy. S° -
hypopituitarism, hypoprolactenemia), estrogen excess (liver failure, tumors, HCG-secreting tumors).
Diagnosis: proper history (usually drugs like spironolactone for cardiac failure, liver cirrhosis). Serum
testosterone, FSH, LH, estradiol, prolactin, HCG.
Treatment: Surgical excision.

11. Impotence
Erectile failure. Causes: anxiety, depression, complication to diabetes mellitus, hypogonadism acromegaly,
anxiety, vascular insufficiency, neuropathic, drugs.
Investigations: Blood glucose, testosterone, FSH LH, prolactin.
Management: If hypogonadism (testosterone), if diabetic neuropathy (oral sildenafil, nitrates are contraindicated
with it), Inj prostaglandin E1, vacuum constriction device, penile prosthesis.

12. Diabetes insipidus

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 • Cranial – deficient production of ADH.
• Nephrogenic – renal tubules unresponsive to ADH.
Causes: Cranial – injury to hypothalamus, genetic defect, idiopathic. Nephro – genetic defect, metabolic
(hypokalemia, hypercalcemia, drugs (lithium etc), poisoning, other disorders (sjogrens syndrome etc).
Clinical features:
Polyuria, polydipsia, patient may pass 5-20 litres of dilute urine with low specific gravity and osmolality.
Investigations:
• Plasma osmolality high, urine osmolality low.
• ADH is not measurable in serum.
• Water Deprivation Test – to differentiate btw the 2 types. (If plasma osmolality >300mOsm/kg
and urine <600mOsm/kg. If desmopressin (ADH analogue) given and; 1. Urine osm>600mOsm kg
– then it is cranial type. 2. If no effect on urine osm – then it is nephrogenic type.
Treatment:
• Desmopressin (for cranial) – via mucous membrane of nose. In sick patients via IM injection.
Tablet has negligible bioavailability.
• Thiazide diuretics (hydrochlorothoazide) – 50-100mg/d – partial response in both kinds.
• Combination of indomethacin-hydrochlorothiazide or indomethacin-amiloride – for nephrogenic
kind.

Adrenocortical Insufficiency
• P° - damage to adrenal gland (Addisons disease).
• S° - damage to pituitary gland/hypothalamus (mineralocorticoids are still produced by renin-angiotensin
system).

13. Addison’s Disease

Low glucocorticoids, low mineralocorticoids, low adrenal hormones, high ACTH (because pituitary is normal).
Clinical features:
Chronic – weakness, weight loss, nausea, vomiting, fever, anorexia, constipation, abdominal pain,
impotence, depression, syncope, myalgia, mental irritability (hyperpigmentation, small heart, vitiligo,
hypotension, general wasting). Acute – circulatory shock, hyponatremia, hyperkalemia, hypoglycemia,
muscle cramps, NVD, fever.
Summary:
• Low glucocorticoids-weakness, hypoglycemia, hypotension, NVD.
• Low mineralocorticoids-low sodium, high potassium, hypotension.
• Hugh ACTH-pigmentation because melanin stimulating hormones is also released.
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 • Low androgens-less body hair.
Investigations:
Blood urea and serum electrolytes (high urea, low sodium, high potassium, high calcium), low blood
sugar, blood CP (neutropenia, eosinophilia, lymphocytosis), xray chest, CT abdomen (small non calcified
adrenals in autoimmune, enlarged in metastatic disease, calcified in TB).
Specific tests include: Serum cortisol, plasma ACTH, ACTH stimulation test (after administration of
ACTH, plasma cortisol does not rise), plasma ACTH (ACTH high and cortisol low or normal), anti
adrenal antibodies (present in 50% cases), aldosterone low and high plasma renin activity.
Treatment: glucocorticoid and mineralocorticoids replacement.
• Glucocorticoids – cortisol (20-25mg daily), prednisolone (7.5mg daily), dexamethasone (0.75mg
daily).
• Mineralocorticoids – fludrocortisone (50-400ug daily).
• Androgens – DHEA (50mg orally each morning).
• If TB is the cause, then anti tuberculous therapy.
Adrenal Crises: Acute adrenal insufficiency. Features – same as that of acute state. Emergency. Investigations
– low blood glucose, low Na, high K, high urea, positive blood culture maybe, low urinary and blood cortisol.
Treatment – inj normal saline (5% dextrose if hypoglycemia), inj hydrocortisone (100mg IV then 100mg 6
hourly for 2 days then shift to oral prednisolone), Antibiotics, management of shock. Complications –
overhydration, hypokalemia, edema, hypertension.

14. Cushing's Syndrome

Excess corticosteroids because of increased ACTH (pituitary adenoma). Common in females.
Causes: Iatrogenic (glucocorticoid therapy), spontaneous (adrenal adenoma/carcinoma, ACTH therapy, ectopic
ACTH syndrome, adrenal hyperplasia). Pseudocushing – cortisol excess as part of another illness.
Clinical features:
Weight gain, centripetal/truncal obesity, menstrual irregularity, plethora hirsutism, moonface,
psychiatric, hypertension, backache, bruising, muscle weakness, pink stretch marks on abdomen, loss of
height, osteoporosis.
Investigations:
Confirmation:
• Overnight low dose dexamethasone suppression test.
• 24 hours urinary free cortisol measurement.
• 48 hours low dose dexamethasone test.
• Circadian rhythm.
After it is confirmed:
• Plasma ACTH level (above 300mg/l) – tumor.

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 • Adrenal CT scan (to detect adenoma/carcinoma).
• Plasma K level (low in ectopic ACTH secretion).
• Corticotrophin releasing hormone test (exaggerated ACTH responses).
• High dose dexamethasone test (failure of cortisol suppression).
Complications: hypertension, diabetes, fractures, Nelson syndrome, psychosis.
Treatment:
• Transphenoidal surgery – resection of pituitary tumor, function returns to normal but ACTH
suppressed and requires 6-36 months to recover so meanwhile hydrocortisone replacement
therapy required.
• Bilateral laproscopic adrenalectomy (if remission occurs after first step)
• Radiotherapy.
• Medical (ketokonazole 200mg 6 hourly).
• Adrenal tumors are resected laproscopically and meanwhile given hydrocortisone replacement
therapy, otherwise drugs.

15. Hypopituitarism
Causes: lesion of hypothalamus – congenital deficiency of pituitary hormones (Kallmans), acquired – head
injury/surgery, syphilis, TB etc. Lesions of pituitary – tumors, surgery, Radiotherapy, head injury, autoimmune,
Hemorrhage in tumor.
Clinical features:
• Growth hormones (GH) Loss – lethargy, muscle weakness, inc fat mass.
• FSH and LH loss – loss of libido, impotence, oligomenorrhea/amenorrhea, gynaecomastia, loss of
hair, wrinkled skin.
• ACTH loss – cortisol deficiency (hypotension, hypoglycemia, nausea, vomiting, skin pallor – lack
of melanin).
• TSH loss – S° hypothyroidism (hypothermia, low metabolic rate, dry skin, constipation).
• Coma (because of hypoglycemia, water intoxication, hypothermia).
Investigations:
Xray skull, MRI scan of brain, pituitary function tests (testosterone, ACTH/cortisol, prolactin, FSH, LH,
T3, T4, GH).
Treatment:
Treatment of underlying causes. Replacement therapy:
• Cortisol – deltacortil 20mg on waking up and 10mg at 6pm.
• Thyroid – thyroxine 0.1-0.5mg once daily.
• Sex hormones – male – depot testosterone esters 250-500mg IM every 2-4 weeks. Female –
estrogen therapy 3 weeks with progesterone for days 14-12 in premenopausal and HCG IM
weekly postmenopausal.
• Adrenal – prednisolone 5-10mg daily.
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 • Growth hormone – recombinant human growth hormone.

16. Prolactinoma
Premenopausal women. Micro adenomas. Associated with GH secreting cells hence may also cause excess GH
leading to acromegaly. Higher prolactin, bigger the tumor.
Investigation is like any other pituitary tumor.
Management:
Medical – dopamine agonist drugs (bromocriptine 2.5-15mg/day 2-3times daily, cabergoline 250-1000ug/week
2 doses/week, quinagolide 50-150ug/day once daily). These shrink the tumor, reduce serum prolactin.
Surgery and radiotherapy – if tumor does not shrink with drugs or patient is intolerant to drugs. Transphenoidal
surgery.
Pregnancy: causes infertility. Patients with micro adenomas should not be given dopamine therapy. With macro
adenomas should not dopamine therapy. With macroprolactinomas, they can. Measurement of prolactin levels
and visual fields.

17. Acromegaly
High GH, growth of bulk of bones not length. After epiphyseal closure (adenoma of pituitary gland) –
macroadenomas(>1cm) Acromegaly, before closure – gigantism. GH stimulates IGF-1.
Clinical features:
Local effects – headache (intrasellar pressure), vomiting, pressure on optic chiasma which leads to
bitemporal hemianopia, cranial nerve palsy, hemiparesis, effects on pituitary cause hypothyroidism,
impotence/amenorrhea.
Increase in GH – skeleton: spade like hands and feet, prognathism, prominent supra orbital ridges, large
frontal sinuses, inc hat size, spacing between teeth, arthropathy, overgrowth of vertical bone – causes
spinal stenosis. Soft tissue: macroglossia (difficult articulation), laryngeal/pharyngeal hypertrophy –
obstructive sleep apnea, thick lips and nose, thick soft tissue of hands and feet, thick skin, inc sweating,
acne, moisture handshake, myopathy, visecromegaly, Carpal tunnel syndrome. Metabolic effects: glucose
intolerance, diabetes mellitus, hypertension, weight gain, hypogonadism (secretion of prolactin,
suppression of pituitary), S° hypothyroidism.
Complications: hypopituitarism, hypertension, glucose intolerance, diabetes mellitus, cardiomegaly, cardiac
failure, arthritis, visual field defects, cranial nerve palsy.
Investigations:
• Fasting serum prolactin raised.
• IGF-1 raised.
• GH (during oral glucose tolerance test) 75g glucose given orally and serum GH measured after 60
min (normal<2mU/l, in acromegaly >2mU/l).
• Pituitary function tests (partial/complete hypopituitarism).
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 • Xrays (enlarged pituitary fossa and double floor. Hands and feet tufting, inc thickness of heel
pad).
• CT scan/MRI (detect tumor extent).
Management:
To reduce GH below 5mU/L.
• Surgery – transphenoidal, transfrontal (for big tumors). Complications: Nausea, vomiting,
seizures, headache, infection, CSF leak, hyponatremia.
• Radiotherapy - 2nd line. If it persists after surgery and medical.
• Medical – Somatostatin analogues: octreotide/ianreotide lower GH but not shrink tumor.
Subcutaneous inj 2-3 times daily then replaced by intra gluteal injection. Dopamine agonists:
bromocriptine 1.25-2.5mg/day inc to 20-30mg/day. GH antagonist: pegvisomant 20mg
subcutaneously daily. In ones where octreotide isn’t effective.

18. Gigantism
Height 7-8ft. Skeletal muscles may be powerfully developed but later weakness develops. May be hypertension.
Xray skull shows enlargement of sella. Treatment is same as that of acromegaly.

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