Learn — Endocrine

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Thyroid eye disease

Thyroid eye disease, also called Graves orbitopathy, is an autoimmune inflammation in which antibodies against the TSH receptor act on orbital fibroblasts, so the extraocular muscles and orbital fat swell and push the eye forward inside a bony socket that cannot expand. It runs its own course of an active inflammatory phase lasting months to about two years followed by an inactive fibrotic phase, which is why it can appear before, during or after the thyroid becomes overactive and does not simply resolve when the thyroid function is corrected.

The signs are proptosis or exophthalmos, upper lid retraction with sclera visible above the cornea (Dalrymple sign), lid lag on looking down (von Graefe sign), infrequent blinking (Stellwag sign), absent forehead wrinkling on upward gaze (Joffroy sign), poor convergence (Mobius sign), periorbital oedema, conjunctival injection and chemosis, and restrictive squint with diplopia.
Lid retraction and lid lag come from sympathetic overactivity and settle as the thyrotoxicosis is treated, while proptosis comes from orbital infiltration and does not reverse with antithyroid drugs; that difference is the most commonly examined discriminator in the topic.
Smoking is the strongest modifiable risk factor, increasing both the risk and the severity and reducing the response to treatment, so structured smoking cessation is part of the prescription rather than general advice.
Radioactive iodine treatment can precipitate or worsen the orbitopathy and steroid cover is given to patients at risk; allowing the patient to become hypothyroid after any definitive treatment also worsens the eyes, so the aim is to reach and hold a euthyroid state.
Activity and severity are graded separately: the Clinical Activity Score out of 7 rates inflammation, with a score of 3 or more taken as active disease, while severity grading rates the threat to sight; visual acuity, colour vision, pupil reactions and corneal staining are recorded at every review.
Mild disease is managed conservatively with artificial tears through the day and lubricating ointment at night, taping the lids or a moisture chamber for incomplete closure, prisms for diplopia, sleeping with the head of the bed raised to reduce morning periorbital swelling, dark glasses, selenium supplementation for a limited course, and smoking cessation.
Moderate to severe active disease is treated with weekly intravenous methylprednisolone pulses over about 12 weeks, with the cumulative dose kept within accepted limits because of hepatotoxicity; orbital radiotherapy, ciclosporin, rituximab and teprotumumab are the second-line options.
Surgery belongs to the inactive phase and is done in a fixed order: orbital decompression first, then squint surgery, then eyelid surgery, because each operation changes the result of the next.
Dysthyroid optic neuropathy and exposure keratopathy with corneal ulceration are the two sight-threatening complications, and they are the reason a patient with thyroid eye disease is asked at every visit about vision rather than only about appearance.

DKA — Kussmaul breathing

Diabetic ketoacidosis is the triad of hyperglycaemia, ketonaemia and high anion gap metabolic acidosis caused by absolute or relative insulin deficiency together with a rise in the counter-regulatory hormones, so that fat is broken down to ketoacids while glucose cannot enter the cell. Kussmaul breathing is the deep, sighing, rapid respiration by which the patient blows off carbon dioxide to compensate for that acidosis, and together with the sweet acetone smell on the breath it is the sign that tells you at the door of the ward that the acidosis is severe.

The classic diagnostic values are a blood glucose above 250 mg/dL, an arterial pH below 7.30, a bicarbonate below 18 mmol/L, an anion gap above 10 to 12, and ketones in blood or urine; euglycaemic ketoacidosis with a glucose below 200 mg/dL occurs with SGLT2 inhibitors, in pregnancy and after starvation, so a normal glucose never excludes the diagnosis.
Severity is graded by the acidosis and the mental state: mild disease has a pH of 7.25 to 7.30 with an alert patient, moderate a pH of 7.00 to just under 7.25 with drowsiness, and severe a pH below 7.00 with stupor or coma.
Precipitating causes are infection first of all, then omitted or interrupted insulin, a first presentation of type 1 diabetes, myocardial infarction, stroke, pancreatitis, corticosteroids and SGLT2 inhibitors, so a source of sepsis is looked for in every case.
Fluid comes before insulin: isotonic 0.9 percent sodium chloride at about 15 to 20 mL per kilogram, usually 1 to 1.5 litres, in the first hour, then 250 to 500 mL per hour adjusted to the corrected sodium, with 5 to 10 percent dextrose added once the glucose falls to 200 to 250 mg/dL so that the insulin infusion can continue clearing ketones.
Insulin is given as a regular insulin infusion at 0.1 units per kilogram per hour, aiming to lower the glucose by about 50 to 75 mg/dL per hour; too rapid a fall risks cerebral oedema, and the infusion is not stopped when the sugar normalises but covered with dextrose until the ketosis clears.
Insulin is never started until the potassium is at least 3.3 mmol/L, because insulin drives potassium into the cell and can cause fatal hypokalaemia and arrhythmia; potassium below 3.3 means hold the insulin and replace potassium first.
Total body potassium is depleted even when the serum value looks normal or high, because acidosis has shifted it out of the cells: with a potassium above 5.2 mmol/L none is given and it is rechecked, between 3.3 and 5.2 mmol/L about 20 to 30 mmol is added to each litre of fluid to hold it between 4 and 5, and hourly to two-hourly monitoring continues throughout.
Bicarbonate is not given routinely and is considered only at a pH below 6.9, because it worsens hypokalaemia, delays ketone clearance and can cause a paradoxical fall in cerebrospinal fluid pH.
Resolution is defined as a glucose below 200 mg/dL together with two of a bicarbonate of 15 mmol/L or more, a venous pH above 7.30 and an anion gap of 12 or less, and subcutaneous insulin is given 1 to 2 hours before the infusion is stopped so that there is no gap in cover.
Hyperosmolar hyperglycaemic state is the differential: glucose usually above 600 mg/dL, effective serum osmolality above 320 mOsm/kg, pH above 7.30, bicarbonate above 18 mmol/L and minimal ketones, developing over days in type 2 diabetes with a higher mortality than ketoacidosis.

Diabetes insipidus

Diabetes insipidus is the passage of large volumes of inappropriately dilute urine because antidiuretic hormone is either not produced by the posterior pituitary (central or cranial disease, now also called arginine vasopressin deficiency) or is produced but ignored by the renal collecting duct (nephrogenic disease, or arginine vasopressin resistance). The danger is not the polyuria itself but the dehydration and hypernatraemia that follow within hours whenever the patient cannot drink to keep up, which is why it kills the unconscious, the very young and the elderly rather than the alert adult with a water bottle.

The diagnostic picture is a urine output above 3 litres a day in an adult (more than about 40 mL per kilogram in 24 hours), a urine specific gravity below 1.005, a urine osmolality below 300 mOsm/kg and often below 200, with a serum osmolality that is high-normal or raised and a serum sodium that is normal or high.
Central causes are head injury, pituitary or hypothalamic surgery, craniopharyngioma and other tumours, infiltrative disease, meningitis, Sheehan syndrome and idiopathic autoimmune disease; nephrogenic causes are lithium, chronic hypokalaemia, hypercalcaemia, obstructive uropathy, chronic kidney disease and inherited receptor defects.
The water deprivation test followed by desmopressin separates the types: in central disease the urine concentrates substantially after desmopressin is given, in nephrogenic disease it does not concentrate with either deprivation or desmopressin, and in primary polydipsia the urine concentrates with deprivation alone.
Central disease is treated with desmopressin by intranasal, oral or parenteral route with free access to water; nephrogenic disease is treated by removing the cause and by a low-salt, low-protein diet with a thiazide diuretic, which paradoxically reduces urine volume through mild volume depletion, with amiloride added for lithium-induced disease.
The discriminator against diabetes mellitus is the urine itself: osmotic diuresis from uncontrolled diabetes mellitus gives glycosuria with a high specific gravity above 1.020 and a high blood glucose, whereas the urine of diabetes insipidus is dilute and sugar-free.
The discriminator against primary polydipsia is the serum sodium: it is low or low-normal in the compulsive water drinker and high-normal or raised in true diabetes insipidus, because the polyuria there is the cause and not the consequence.
After pituitary surgery a triphasic response is classic: diabetes insipidus in the first 24 hours, then a phase of antidiuresis at about days 5 to 10 in which continued desmopressin causes dangerous hyponatraemia, then permanent diabetes insipidus.
Nursing management is measurement: strict hourly intake and output, hourly urine specific gravity, daily weight at the same time on the same scale, serum sodium and osmolality as ordered, water within reach at all times, and fall precautions for a patient who is up all night passing urine.

Diabetes mellitus — management

Diabetes mellitus is a group of metabolic disorders of chronic hyperglycaemia resulting from defective insulin secretion, defective insulin action or both, and its management is the lifelong package of nutrition, activity, drugs, self-monitoring, education and complication screening rather than the prescription alone. It matters more in India than almost anywhere because Indians develop it a decade earlier and at a lower body mass index than western populations, so the screening thresholds and the targets used in the examination are the Asian-Indian ones.

Diagnosis needs any one of a fasting plasma glucose of 126 mg/dL or more after an 8-hour fast, a 2-hour value of 200 mg/dL or more in a 75 g oral glucose tolerance test, an HbA1c of 6.5 percent or more, or a random glucose of 200 mg/dL or more with classical symptoms; in the absence of unequivocal symptoms the abnormal result is confirmed by a repeat test.
Prediabetes is a fasting glucose of 100 to 125 mg/dL (impaired fasting glucose), a 2-hour value of 140 to 199 mg/dL (impaired glucose tolerance) or an HbA1c of 5.7 to 6.4 percent, and it is treated with structured lifestyle change because progression to diabetes is preventable at this stage.
Glycaemic targets for most non-pregnant adults are an HbA1c below 7 percent, a preprandial capillary glucose of 80 to 130 mg/dL and a peak postprandial value below 180 mg/dL; a tighter target below 6.5 percent suits the young and newly diagnosed if it can be reached without hypoglycaemia, and a looser target of about 8 percent suits the elderly, those with hypoglycaemia unawareness, advanced complications or limited life expectancy.
Metformin remains the usual first-line drug, started at 500 mg once or twice daily with meals and titrated up; it is not started when the estimated glomerular filtration rate is below 45 and is stopped below 30 mL per minute per 1.73 square metres, is withheld before contrast imaging and during acute illness or dehydration because of lactic acidosis, and causes vitamin B12 deficiency with long use.
Certain drugs are added for the organ, not for the sugar: an SGLT2 inhibitor for heart failure, chronic kidney disease or established atherosclerotic disease, and a GLP-1 receptor agonist for atherosclerotic disease and for weight, both given regardless of whether the HbA1c is at target. SGLT2 inhibitors cause genital mycotic infection, volume depletion and euglycaemic ketoacidosis, so they are withheld before surgery and during acute illness.
Sulfonylureas and insulin are the agents that cause hypoglycaemia, and sulfonylureas and pioglitazone cause weight gain, while metformin, DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists do not cause hypoglycaemia when used alone.
Insulin technique is examinable: a rapid-acting analogue is given 0 to 15 minutes before the meal and regular human insulin 30 minutes before, NPH peaks at about 4 to 10 hours and causes nocturnal hypoglycaemia, glargine and degludec have no pronounced peak; injection sites are rotated within one region to prevent lipohypertrophy, absorption is fastest from the abdomen, unopened vials and pens are stored at 2 to 8 degrees Celsius and never frozen, and the in-use pen is kept at room temperature for up to about 4 weeks.
Hypoglycaemia is a glucose below 70 mg/dL, is clinically significant below 54 mg/dL, and is treated by the rule of 15 in a conscious patient: 15 g of fast-acting carbohydrate such as 3 teaspoons of glucose or sugar, recheck after 15 minutes, repeat if still low, then give a meal or snack; an unconscious patient receives 25 mL of 50 percent dextrose intravenously or glucagon 1 mg intramuscularly when there is no line.
Complication screening is scheduled, not opportunistic: a dilated retinal examination at diagnosis in type 2 diabetes and 5 years after diagnosis in type 1, then annually; urine albumin-to-creatinine ratio and estimated glomerular filtration rate every year; and an annual foot examination with the 10 g monofilament and vibration testing, with daily self-inspection, never walking barefoot, no hot water bottles and nails cut straight across.
Indian practice points: overweight begins at a body mass index of 23 and obesity at 25 kg per square metre for Asian Indians, with waist circumference cut-offs of 90 cm in men and 80 cm in women, at least 150 minutes of moderate physical activity a week spread over at least three days with no more than two consecutive days without exercise, and population-based screening from the age of 30 through the Community Based Assessment Checklist under the national non-communicable disease programme.

Simmonds disease (panhypopituitarism)

Simmonds disease is panhypopituitarism — failure of the anterior pituitary to secrete its trophic hormones, so the thyroid, the adrenal cortex and the gonads all shut down together, with growth hormone and prolactin lost as well. In Indian obstetric practice its commonest form is Sheehan syndrome, in which severe postpartum haemorrhage causes ischaemic necrosis of the enlarged pituitary, and the first sign is a mother who cannot produce milk.

The hormones are lost in a fairly constant order — growth hormone first, then LH and FSH, then TSH, then ACTH, with prolactin usually last; the exception is Sheehan syndrome, where failure of lactation from prolactin loss is the earliest complaint.
Sheehan syndrome follows a postpartum haemorrhage severe enough to cause hypotension: no lactation, no return of menses, loss of axillary and pubic hair, fatigue, cold intolerance and postural hypotension appearing over weeks to years.
The biochemical signature is a low target-gland hormone with a low or inappropriately normal trophic hormone — a low free T4 with a TSH that is normal instead of raised is the classic trap, so a normal TSH never excludes central hypothyroidism.
Hyponatraemia and hypoglycaemia are typical; hyperkalaemia and skin hyperpigmentation are NOT, because aldosterone is driven by renin-angiotensin rather than by ACTH and there is no excess ACTH to darken the skin — that is what separates secondary from primary (Addison) adrenal failure.
MRI of the pituitary shows an empty sella in established Sheehan syndrome, and dynamic testing such as the short Synacthen or insulin tolerance test confirms which axis has failed.
Replacement is lifelong: hydrocortisone about 15 to 25 mg a day in divided doses, levothyroxine titrated to the free T4 and never to the TSH, oestrogen-progestogen or testosterone for the gonadal axis, and growth hormone in selected patients.
Glucocorticoid is always started before levothyroxine, because thyroxine raises the metabolic clearance of cortisol and can precipitate an adrenal crisis in an untreated patient.
Sick-day rules are taught before discharge: double the hydrocortisone during fever or illness, take it by injection if vomiting, and carry a steroid alert card, because an intercurrent infection is what turns a stable patient into an adrenal crisis.

Hypoparathyroidism vs hyperparathyroidism

Parathyroid hormone raises serum calcium — it pulls calcium out of bone, reabsorbs it in the distal tubule and activates vitamin D in the kidney — while it dumps phosphate into the urine. Hypoparathyroidism therefore gives a low calcium with a HIGH phosphate and hyperparathyroidism gives a high calcium with a LOW phosphate, and that single mirror-image pair of values decides almost every examination question and every bedside decision on this topic.

Hypoparathyroidism: low PTH, serum calcium below 8.5 mg/dL, raised phosphate and a prolonged QT interval on the ECG; the commonest cause is accidental removal of or injury to the parathyroids during thyroid surgery, and the hypocalcaemia typically appears 24 to 72 hours after the operation.
The bedside signs of hypocalcaemia are perioral and fingertip tingling, carpopedal spasm, Chvostek sign (tapping the facial nerve in front of the ear twitches the lip) and Trousseau sign (a cuff inflated above systolic for 3 minutes produces carpal spasm); Trousseau is the more specific of the two.
Acute tetany is treated with 10 mL of 10% calcium gluconate diluted and given slowly intravenously over about 10 minutes with cardiac monitoring, followed by an infusion; long-term treatment is oral calcium with ACTIVE vitamin D (calcitriol), because plain vitamin D cannot be 1-alpha-hydroxylated without PTH.
Hypocalcaemia that will not correct with calcium is hypomagnesaemia until proved otherwise — a low magnesium blocks both the release and the action of PTH, so the magnesium has to be replaced before the calcium will rise.
Primary hyperparathyroidism is a single adenoma in about 85% of cases: high calcium, low phosphate, a PTH that is raised or inappropriately normal for that calcium, a raised alkaline phosphatase and high urinary calcium.
The syndrome is remembered as painful bones, renal stones, abdominal groans and psychic moans — osteitis fibrosa cystica with brown tumours and subperiosteal resorption on the radial side of the middle phalanges, calcium stones and nephrocalcinosis, constipation, peptic ulcer and pancreatitis, and depression or confusion; the ECG shows a SHORT QT.
Parathyroidectomy is the only cure, and in an asymptomatic patient it is offered when the calcium is more than 1 mg/dL above the upper limit of normal, the eGFR is under 60 mL/min/1.73 m2, there are stones or nephrocalcinosis, the bone density T-score is -2.5 or worse or there is a vertebral fracture, or the patient is under 50 years old.
Secondary hyperparathyroidism (chronic kidney disease, vitamin D deficiency) has a LOW or normal calcium with a high PTH; tertiary hyperparathyroidism is the autonomous gland that follows years of secondary disease and has a HIGH calcium with a very high PTH.
Hungry bone syndrome after parathyroidectomy causes profound hypocalcaemia in the first 24 to 72 hours as the demineralised skeleton takes calcium back — check serum calcium every 6 to 12 hours and watch for tingling, spasm and stridor.

Graves disease

Graves disease is autoimmune hyperthyroidism caused by an IgG antibody that stimulates the TSH receptor, so the whole gland is driven to make thyroid hormone with no control from the pituitary. It is the commonest cause of thyrotoxicosis in young women, and it is the only cause that also produces eye disease, pretibial myxoedema and thyroid acropachy, because the same antibody attacks retro-orbital and dermal fibroblasts.

The biochemical picture is a suppressed TSH, often below 0.01 mIU/L, with a raised free T4 and free T3 and a positive TSH-receptor antibody (TRAb); TRAb is what confirms Graves rather than any other cause of thyrotoxicosis.
A radioiodine uptake scan is the discriminator when antibodies are unavailable: Graves shows diffuse INCREASED uptake, while thyroiditis and factitious thyrotoxicosis show LOW or absent uptake — and their treatments are completely different.
Signs unique to Graves are a diffuse goitre with a bruit, orbitopathy with proptosis, lid retraction and lid lag, pretibial myxoedema over the shins and thyroid acropachy; weight loss with a good appetite, heat intolerance, tremor, palpitations and atrial fibrillation come from the thyrotoxicosis itself.
First-line drug treatment in India is carbimazole or methimazole 10 to 40 mg a day for 12 to 18 months, with propranolol 20 to 40 mg every 6 to 8 hours for tremor, tachycardia and anxiety while the thionamide takes its 4 to 8 weeks to work.
Propylthiouracil is preferred in the first trimester of pregnancy because methimazole and carbimazole are associated with aplasia cutis and choanal atresia, and it is switched back after the first trimester because propylthiouracil can cause fulminant hepatic failure.
The instruction that saves lives is that any sore throat, mouth ulcer or fever while taking carbimazole or propylthiouracil means stopping the drug and getting an urgent total and differential white cell count, because agranulocytosis is idiosyncratic and can appear at any dose.
Radioiodine is definitive but is absolutely contraindicated in pregnancy and breastfeeding, requires pregnancy to be avoided for about 6 months afterwards, worsens active eye disease unless steroid cover is given, and leaves most patients permanently hypothyroid on levothyroxine.
Total thyroidectomy is chosen for a large compressive goitre, suspected malignancy, severe eye disease or drug failure; the patient is made euthyroid first and given Lugol iodine for 10 to 14 days before surgery to reduce the vascularity of the gland.

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