Hypopituitarism is the deficient production of one or more pituitary hormones, and many conditions can cause that failure. The causes divide first by timing. Congenital causes are present before or around birth and usually work through a mutation in a receptor, a transcription factor (a protein that switches on the genes a cell needs to develop) or a hormone itself. Acquired causes damage a previously normal gland later in life, either by compressing it from a tumour in or around the sella (the bony hollow at the skull base that holds the pituitary), by interrupting its blood supply, by inflammation or infiltration, by infection, or by irradiation. Either group may affect a single hormone lineage (one type of hormone-producing cell) or several together.
Two entries in the classification carry most of the weight in practice. A pituitary adenoma is the most common cause of adult-onset hypopituitarism, and a craniopharyngioma, which arises from remnants of Rathke’s pouch (the embryonic pouch from which the anterior pituitary forms), is more common in children. Several of the congenital entries are syndromes in which the endocrine failure is only one part of a wider phenotype.
The full classification, with examples in each category, is given below. In the congenital rows, isolated deficiency means a single pituitary hormone is lost and multiple deficiency means several are lost together.
| Category | Subtype | Examples |
|---|---|---|
| Congenital | Isolated pituitary hormone deficiency | Receptor mutation: GHRH, CRH, GnRH, TRH receptor mutations Transcription factor defect: PITX2, TBX19, DAX1, NR5A1, NR0B1 Hormone mutation: GH1, bio-inactive GH, FSHb, LHb, TSHb, POMC, POMC processing defect Prader-Willi syndrome Bardet-Biedl syndrome Kallmann syndrome |
| Multiple pituitary hormone deficiency | Transcription factor defect: HESX1, SOX 2/3, LHX3/4, PROP1, POU1F1, IGSF1 mutations Prohormone convertase enzyme mutation: PC1 | |
| Neoplastic | Pituitary adenoma | Functioning and non-functioning |
| Peri-pituitary tumours | Parasellar lesion: craniopharyngioma, Rathke’s cleft cyst Non-adenomatous neoplasm: meningioma, glioma, germ cell tumour Metastases, especially breast, renal, bronchus | |
| Vascular | Infarction/haemorrhage | Sheehan’s syndrome Pituitary apoplexy Aneurysms |
| Inflammatory / infiltrative / immunological | Hypophysitis: lymphocytic, granulomatous, xanthomatous, necrotising, IgG4-related, immunotherapy-induced (CTLA-4 inhibitors), other immune-associated Haemochromatosis Sarcoidosis Wegener’s granulomatosis Giant cell granuloma Langerhans cell histiocytosis | |
| Infectious | Bacterial: tuberculosis, syphilis, leptospirosis Fungal: candidiasis, aspergillosis Viral: herpes/varicella infection, SARS-CoV-2 virus | |
| Post-irradiation | Pituitary Nasopharyngeal Cranial | |
| Miscellaneous | Empty sella Traumatic brain injury Medications |
The congenital rows raise the question of where the fault lies: in the way the pituitary itself forms and differentiates, or in the hypothalamic signals that drive it.