Endocrine Disorders
Endocrine Disorders: Hypo- and Hyperfunction by Gland
| Gland/Organ | Hypofunction Disorders (↓ Hormones) | Hyperfunction Disorders (↑ Hormones) |
|---|---|---|
| Hypothalamus | – Kallmann syndrome (GnRH ↓) – Functional hypothalamic amenorrhoea – Hypothalamic obesity | – Hypothalamic hamartoma (GnRH ↑ → precocious puberty) |
| Pituitary (Anterior) | – Hypopituitarism – Sheehan syndrome – Empty sella syndrome – Pituitary apoplexy | – Prolactinoma (↑ Prolactin) – Acromegaly (↑ GH) – Cushing’s disease (↑ ACTH) – TSH-secreting adenoma |
| Pituitary (Posterior) | – Diabetes insipidus (↓ ADH) | – SIADH (↑ ADH) |
| Thyroid | – Hashimoto’s thyroiditis – Iodine deficiency – Post-surgical hypothyroidism – Congenital hypothyroidism – Central hypothyroidism (pituitary) | – Graves’ disease – Toxic multinodular goitre – Toxic adenoma – Subacute thyroiditis (early phase) – Factitious thyrotoxicosis |
| Parathyroid | – Hypoparathyroidism (surgical, autoimmune) – Pseudohypoparathyroidism | – Primary hyperparathyroidism (adenoma) – Secondary hyperparathyroidism (CKD) – Tertiary hyperparathyroidism (CKD with autonomy) |
| Adrenal Cortex | – Addison’s disease (Primary adrenal insufficiency) – Secondary adrenal insufficiency (pituitary/iatrogenic) – Congenital adrenal hyperplasia (salt-wasting forms) | – Cushing’s syndrome – Conn’s syndrome (primary hyperaldosteronism) – CAH (androgen excess) – Adrenocortical carcinoma |
| Adrenal Medulla | No defined hypo-disorder | – Phaeochromocytoma – Paraganglioma (↑ catecholamines) |
| Pancreas (Endocrine) | – Type 1 diabetes mellitus (absolute insulin deficiency) – Maturity-onset diabetes of the young (MODY) | – Insulinoma (↑ insulin → hypoglycaemia) – Islet cell tumours (e.g., glucagonoma, gastrinoma) |
| Ovaries | – Premature ovarian insufficiency – Hypogonadotropic hypogonadism – Turner syndrome | – Polycystic ovary syndrome (↑ androgens, oestrogen) – Ovarian tumours (e.g., granulosa cell tumour) |
| Testes | – Primary hypogonadism (Klinefelter syndrome) – Secondary hypogonadism (pituitary) | – Androgen-producing tumours (Leydig cell) |
| Multiple Glands (Syndromes) | – Autoimmune polyendocrine syndrome (Type 1 & 2) – MEN syndromes with gland failure (rare) | – MEN 1: Pituitary, pancreatic, parathyroid tumours – MEN 2A/B: Medullary thyroid carcinoma, phaeochromocytoma, parathyroid hyperplasia |
Endocrine Disorders Organised by Hormonal Axis
| Hormonal Axis | Hypofunction (↓ hormones) | Hyperfunction (↑ hormones) |
|---|---|---|
| Hypothalamic-Pituitary-Adrenal (HPA) Axis CRH → ACTH → Cortisol | – Addison’s disease (Primary adrenal insufficiency) – Secondary adrenal insufficiency (↓ ACTH, e.g. pituitary failure) – Tertiary adrenal insufficiency (↓ CRH, e.g. exogenous steroid suppression) | – Cushing’s syndrome (endogenous or iatrogenic) • ACTH-dependent: Cushing’s disease (pituitary) • ACTH-independent: adrenal adenoma/carcinoma • Ectopic ACTH (e.g. small cell lung cancer) |
| Hypothalamic-Pituitary-Thyroid (HPT) Axis TRH → TSH → T3/T4 | – Primary hypothyroidism (Hashimoto’s, iodine deficiency, post-radioiodine/surgery) – Secondary hypothyroidism (↓ TSH – pituitary) – Tertiary hypothyroidism (↓ TRH – hypothalamus) – Congenital hypothyroidism | – Graves’ disease (autoimmune TSH receptor stimulation) – Toxic multinodular goitre – Toxic adenoma – TSH-secreting pituitary adenoma – Thyroiditis (early phase) |
| Hypothalamic-Pituitary-Gonadal (HPG) Axis GnRH → LH/FSH → Oestrogen/Testosterone | – Hypogonadotropic hypogonadism (stress, weight loss, pituitary tumour) – Primary hypogonadism: • Turner syndrome (XO) • Klinefelter syndrome (XXY) – Premature ovarian insufficiency – Anorchia – Functional hypothalamic amenorrhoea | – Polycystic ovary syndrome (PCOS) (↑ LH, androgens) – Oestrogen/testosterone-secreting tumours – Congenital adrenal hyperplasia (via androgen excess) |
| Growth Hormone Axis GHRH → GH → IGF-1 (liver) | – GH deficiency (childhood: dwarfism; adults: fatigue, ↑ fat mass) – Pituitary damage/apoplexy – Laron syndrome (GH resistance) | – Acromegaly (GH-secreting pituitary adenoma – after epiphyseal closure) – Gigantism (before epiphyseal closure) – Ectopic GHRH secretion (rare) |
| Prolactin Axis TRH → Prolactin (inhibited by dopamine) | – Hypoprolactinaemia (rare; lactation failure post-partum) – Dopamine agonist excess (e.g. cabergoline) | – Prolactinoma – Drug-induced hyperprolactinaemia (antipsychotics, SSRIs, domperidone) – Hypothyroidism (via ↑ TRH stimulation) |
| Posterior Pituitary – ADH Axis Osmoreceptors → ADH (vasopressin) | – Diabetes insipidus (central or nephrogenic) • Central: ↓ ADH (e.g. trauma, tumour) • Nephrogenic: ADH resistance (e.g. lithium, hypercalcaemia) | – SIADH (Syndrome of Inappropriate ADH Secretion) • CNS pathology, malignancy (SCLC), medications |
| Calcium–Parathyroid Axis Ca2+ → PTH → Bone/kidney/vitamin D | – Hypoparathyroidism (post-surgical, autoimmune) – Pseudohypoparathyroidism (resistance to PTH) | – Primary hyperparathyroidism (adenoma/hyperplasia) – Secondary hyperparathyroidism (CKD-induced) – Tertiary hyperparathyroidism (autonomous PTH in CKD) |
| Pancreatic Islet Axis Glucose → Insulin/glucagon | – Type 1 diabetes mellitus (autoimmune β-cell destruction) – Latent autoimmune diabetes in adults (LADA) – MODY | – Insulinoma (→ recurrent hypoglycaemia) – Glucagonoma, somatostatinoma, gastrinoma (as part of NETs or MEN1) |
| Multi-Axis Disorders (MEN/Autoimmune syndromes) | – Autoimmune polyendocrine syndromes (APS type 1 & 2) • Addison’s + T1DM + hypothyroidism ± others | – MEN1: Pituitary, pancreatic NETs, parathyroid hyperplasia – MEN2A/2B: Medullary thyroid carcinoma, phaeochromocytoma, parathyroid hyperplasia |
Notes:
- Primary endocrine disorders: dysfunction at the target gland (e.g. adrenal, thyroid)
- Secondary: pituitary failure (e.g. ↓ ACTH → low cortisol)
- Tertiary: hypothalamic dysfunction
MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES
| Hypofunction (↓ hormones) | Hypofunction (↓ hormones) |
| – Autoimmune polyendocrine syndromes (APS type 1 & 2) • Addison’s + T1DM + hypothyroidism ± others | – MEN1: Pituitary adenoma, parathyroid hyperplasia, pancreatic NETs (e.g. gastrinoma, insulinoma) – MEN2A: Pituitary adenoma, parathyroid hyperplasia, pancreatic NETs (e.g. gastrinoma, insulinoma) – MEN2B: Medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas, marfanoid habitus |
SYSTEMIC OR IATROGENIC ENDOCRINE CONDITIONS
- Steroid-induced Cushing’s syndrome
- Medication-induced hypothyroidism (e.g. amiodarone, lithium)
- Hormone resistance syndromes (e.g. pseudohypoparathyroidism)
- Endocrine paraneoplastic syndromes
- Ectopic hormone secretion (e.g. ACTH, PTHrP)
- Neuroendocrine tumours (NETs)
Clinical Tip: Recognising Patterns
| Presentation | Likely System |
|---|---|
| Polyuria/polydipsia | Pituitary (DI), Pancreas (diabetes) |
| Fatigue & weight loss | Adrenal (Addison’s), Thyroid (hypo) |
| Amenorrhoea | Hypothalamus, Pituitary, Ovaries |
| Hypertension with hypokalaemia | Conn’s syndrome |
| Recurrent hypoglycaemia | Insulinoma, Addison’s |
| Mixed endocrinopathies | MEN syndromes, Autoimmune polyendocrinopathy |
Key Diagnostic Tests by Hormonal Axis
🔷 1. HPA Axis (Hypothalamic–Pituitary–Adrenal)
🟡 Hypofunction (↓ cortisol): Addison’s, Secondary/Tertiary AI
– Addison’s disease (Primary adrenal insufficiency)
– Secondary adrenal insufficiency (↓ ACTH, e.g. pituitary failure)
– Tertiary adrenal insufficiency (↓ CRH, e.g. exogenous steroid suppression)
| Test | Used For | Interpretation |
|---|---|---|
| Morning serum cortisol | Initial screen for insufficiency | <140–170 nmol/L = suspicious for AI |
| Short Synacthen test | Confirm adrenal insufficiency | <500–550 nmol/L at 30/60 min = AI |
| Plasma ACTH | Differentiate primary vs secondary | ↑ ACTH = Addison’s ↓ ACTH = secondary/tertiary |
| Renin & Aldosterone | Assess mineralocorticoid function | ↑ Renin + ↓ Aldosterone = Addison’s |
🔴 Hyperfunction (↑ cortisol): Cushing’s syndrome
– Cushing’s syndrome (endogenous or iatrogenic)
• ACTH-dependent: Cushing’s disease (pituitary)
• ACTH-independent: adrenal adenoma/carcinoma
• Ectopic ACTH (e.g. small cell lung cancer)
| Test | Used For | Interpretation |
|---|---|---|
| Low-dose dexamethasone suppression test (1 mg overnight) | Screens for Cushing’s | No suppression = Cushing’s (Cortisol >50 nmol/L = Cushing’s likely) |
| 24h urinary free cortisol | Confirm Cushing’s | ↑ = Cushing’s (>3× ULN = consistent) |
| Late-night salivary cortisol | Sensitive screen – Assess circadian rhythm | ↑ = Cushing’s (Loss of diurnal drop = Cushing’s) |
| Plasma ACTH | Differentiates primary vs secondary AI | ↓ ACTH = Secondary adrenal insufficiency (pituitary cause -Pituitary fails to secrete ACTH → ↓ cortisol ) Tertiary adrenal insufficiency (hypothalamic cause- CRH deficiency → ↓ ACTH → ↓ cortisol) ACTH-independent Cushing’s syndrome (adrenal adenoma/carcinoma – Cortisol excess suppresses ACTH via negative feedback) ↑ ACTH = Primary adrenal insufficiency (Addison’s disease – Adrenal gland failure → ↓ cortisol → loss of negative feedback → ↑ ACTH) ACTH-dependent Cushing’s syndrome (Cushing’s disease or ectopic ACTH- Excess ACTH from pituitary (Cushing’s disease) or ectopic source (e.g., small cell lung carcinoma)) |
| High-dose dexamethasone suppression test | Localise source | Suppression = pituitary (Cushing’s disease) No suppression = ectopic or adrenal |
🔷 2. HPT Axis (Hypothalamic–Pituitary–Thyroid)
🟡 Hypofunction (↓ T3/T4): Hypothyroidism
– Primary hypothyroidism (Hashimoto’s, iodine deficiency, post-radioiodine/surgery)
– Secondary hypothyroidism (↓ TSH – pituitary)
– Tertiary hypothyroidism (↓ TRH – hypothalamus)
– Congenital hypothyroidism
| Test | Used For | Interpretation |
|---|---|---|
| TSH | Initial test | ↑ TSH = primary hypothyroidism ↓ TSH = central |
| Free T4 | Confirm diagnosis | ↓ in all forms of hypothyroidism |
| Anti-TPO Ab | Autoimmune thyroiditis | Positive = Hashimoto’s thyroiditis |
🔴 Hyperfunction (↑ T3/T4): Hyperthyroidism
– Graves’ disease (autoimmune TSH receptor stimulation)
– Toxic multinodular goitre
– Toxic adenoma
– TSH-secreting pituitary adenoma
– Thyroiditis (early phase)
| Test | Used For | Interpretation |
|---|---|---|
| TSH | Initial test | ↓ TSH = primary hyperthyroidism |
| Free T3/T4 | Confirm diagnosis | ↑ in hyperthyroidism |
| TRAb (TSI) | Graves’ disease | Positive = diagnostic |
| Thyroid scan (scintigraphy) | Determine aetiology | Diffuse = Graves’, focal = adenoma, low uptake = thyroiditis |
🔷 3. HPG Axis (Hypothalamic–Pituitary–Gonadal)
🟡 Hypofunction: Hypogonadism, delayed puberty
– Hypogonadotropic hypogonadism (stress, weight loss, pituitary tumour)
– Primary hypogonadism:
• Turner syndrome (XO)
• Klinefelter syndrome (XXY)
– Premature ovarian insufficiency
– Anorchia
– Functional hypothalamic amenorrhoea
| Test | Used For | Interpretation |
|---|---|---|
| LH, FSH | Assess pituitary drive | ↓ = central, ↑ = primary gonadal failure |
| Oestradiol / Testosterone | Confirm sex steroid status | ↓ in hypogonadism |
| Karyotype | Identify genetic cause | Turner (XO), Klinefelter (XXY) |
| GnRH stimulation test | Pubertal evaluation | ↑ LH/FSH = central; no rise = peripheral |
🔴 Hyperfunction: PCOS, virilising tumours
– Polycystic ovary syndrome (PCOS) (↑ LH, androgens)
– Oestrogen/testosterone-secreting tumours
– Congenital adrenal hyperplasia (via androgen excess)
| Test | Used For | Interpretation |
|---|---|---|
| LH:FSH ratio | PCOS assessment | ↑ LH:FSH (>2:1) suggestive of PCOS |
| Total Testosterone | Assess androgen excess | Mild ↑ = PCOS; marked ↑ = tumour |
| DHEAS | Adrenal androgen source | ↑ suggests adrenal origin |
| Pelvic ultrasound | PCOS morphology | >12 follicles per ovary or volume >10 mL |
🔷 4. GH/IGF-1 Axis
🟡 Hypofunction: GH deficiency
– GH deficiency (childhood: dwarfism; adults: fatigue, ↑ fat mass)
– Pituitary damage/apoplexy
– Laron syndrome (GH resistance)
| Test | Used For | Interpretation |
|---|---|---|
| IGF-1 | Screening | ↓ IGF-1 = possible GH deficiency |
| GH stimulation test (e.g., insulin tolerance test) | Confirm | Blunted GH rise = deficiency |
🔴 Hyperfunction: Acromegaly/Gigantism
– Acromegaly (GH-secreting pituitary adenoma – after epiphyseal closure)
– Gigantism (before epiphyseal closure)
– Ectopic GHRH secretion (rare)
| Test | Used For | Interpretation |
|---|---|---|
| IGF-1 | Screening | ↑ IGF-1 = acromegaly |
| GH suppression test (OGTT) | Confirm | GH fails to suppress <1 µg/L = acromegaly |
| Pituitary MRI | Localise adenoma | Confirms macro/microadenoma |
🔷 5. Posterior Pituitary – ADH Axis
🟡 Hypofunction: Diabetes insipidus
– Diabetes insipidus (central or nephrogenic)
• Central: ↓ ADH (e.g. trauma, tumour)
• Nephrogenic: ADH resistance (e.g. lithium, hypercalcaemia)
| Test | Used For | Interpretation |
|---|---|---|
| Serum Na, plasma/urine osmolality | Screen | ↑ Na, ↓ urine osmol = DI |
| Water deprivation test | Confirm | Central: ↑ urine osmol after desmopressin Nephrogenic: no change |
🔴 Hyperfunction: SIADH
– SIADH (Syndrome of Inappropriate ADH Secretion)
• CNS pathology, malignancy (SCLC), medications
| Test | Used For | Interpretation |
|---|---|---|
| Serum Na, urine osmol | Diagnose SIADH | ↓ Na, ↑ urine osmol (>100 mOsm/kg) |
| Serum uric acid | Supportive | Often ↓ in SIADH |
🔷 6. Calcium–PTH Axis
🟡 Hypofunction: Hypoparathyroidism
– Hypoparathyroidism (post-surgical, autoimmune)
– Pseudohypoparathyroidism (resistance to PTH)
| Test | Used For | Interpretation |
|---|---|---|
| Serum calcium & phosphate | Assess calcium balance | ↓ Ca, ↑ PO4 = hypoPTH |
| Serum PTH | Confirm | ↓ in hypoparathyroidism |
| Magnesium | Rule out secondary cause | Low Mg may suppress PTH release |
🔴 Hyperfunction: Primary/Secondary HPT
– Primary hyperparathyroidism (adenoma/hyperplasia)
– Secondary hyperparathyroidism (CKD-induced)
– Tertiary hyperparathyroidism (autonomous PTH in CKD)
| Test | Used For | Interpretation |
|---|---|---|
| Serum calcium | Initial screen | ↑ Ca in primary HPT |
| PTH | Confirm diagnosis | ↑ or inappropriately normal in hyperCa |
| 25(OH) Vitamin D | Assess status | Often ↓ in secondary HPT |
| Sestamibi scan | Localise adenoma | Positive in primary HPT |
🔷 7. Pancreatic Islet Axis
🟡 Hypofunction: Type 1 Diabetes, LADA
– Type 1 diabetes mellitus (autoimmune β-cell destruction)
– Latent autoimmune diabetes in adults (LADA)
– MODY
| Test | Used For | Interpretation |
|---|---|---|
| Fasting glucose / HbA1c | Diagnose diabetes | FPG ≥7.0 mmol/L, HbA1c ≥6.5% |
| C-peptide | Assess insulin production | ↓ in T1DM |
| Anti-GAD, anti-IA2 | Autoimmune diabetes | Positive in T1DM or LADA |
🔴 Hyperfunction: Insulinoma
– Insulinoma (→ recurrent hypoglycaemia)
– Glucagonoma, somatostatinoma, gastrinoma (as part of NETs or MEN1)
| Test | Used For | Interpretation |
|---|---|---|
| Supervised 72h fast | Diagnose insulinoma | Hypoglycaemia + ↑ insulin + ↑ C-peptide |
| Proinsulin | Further confirmation | Elevated in insulinoma |
| Imaging (CT/MRI/EUS) | Localise tumour | Needed after biochemical diagnosis |