Hypothalamic-Pituitary hormones

Classification - Pituitary hormone (hypothalamic hormone, target organ hormone)

Adenohypophysis (anterior lobe)

• Gonadotroph - LH/FSH (GnRH, testosterone/estrogen)
• Somatotroph - GH (Somatostatin, GHRH)
• Lactotrope - Prolactin
• Corticotrope - ACTH (CRH, Cortisol)
• Thyrotrope - TSH (FT4, FT3, TRH)

Neurohypophysis (posterior lobe)

• ADH
• Oxytocin

Classification (by site of dysfunction)

• Primary - due to abnormality of secreting target organ e.g. Grave's disease, Hashimoto's thyroiditis
• Secondary - due to abnormality of pituitary e.g. panhypopituitarism, prolactinoma
• Tertiary - due to abnormality of hypothalamus

 In clinical practice there is no requirement to distinguish secondary from tertiary causes or to measure hypothalamic hormones directly

Secondary (pituitary) may or may not involve one hypersecreting endocrine cell with a variable failures of the other cell lines.

Panhypopituitarism involves failure of most or all of the cell lines.

Symptomatology

• Symptoms may not all be present and often non-specific and gradual in onset
• Florid symptoms are not common but may occur in prolonged unmanaged disease or abrupt endocrine failure
• A high reasonable degree of clinical suspicion may be needed
• Screening tests may be required to confirm diagnosis

Pathophysiology and interpretation of tests

• 'Normal' ranges for serum hormone levels are not as tightly regulated or easily defined (unlike other physiological parameters such as BP, serum sodium, pCO2).
• Levels can vary due to diurnal changes or non-endocrine illness (eg. cortisol, thyroid hormone)
• Lab results need to be reconciled with the clinical picture and the likely cause e.g. target organ (Primary) versus sellar mass (Secondary/Tertiary)
• It is usually easy to interpret gross abnormalities if there is complete endocrine failure
• Partial failure of endocrine secretion (primary, secondary, or tertiary) makes interpreting tests difficult because of more subtle changes (always go back to the clinical picture)
• Non-endocrine illness can cause various primary, secondary or tertiary supression or lowered responsiveness without being clinically significant. Diagnosis can be challenging to distinguish the effects of this and true illness. DO NOT OVERTREAT

General rule of interpretation

• Overactivity - ^ secretion target organ hormone
• Underactivity - v secretion target organ hormone

• Primary overactivity - pituitary/hypothalamic suppression (e.g. ^ FT4/v TSH, ^ cortisol/ v ACTH)
• Primary underactivity - pituitary/hypothalamic stimulation
• Secondary overactivity - LACK of pituitary/hypothalamic suppression *
• Secondary underactivity - LACK of pituitary/hypothalamic responsiveness *

* Sometime the magnitudes of changes don't go beyond the normal range

Provocation tests (to confirm diagnosis and differentiate primary from secondary/tertiary causes)

• Overactivity - attempt to block secretion by supression of feedback mechanism at HP axis (e.g. dexamethasone suppression test)
  Underactivity - attempt to promote secretion by stimulation of feedback mechanism (e.g. insulin/hypoglycaemic test)

Screening tests

• Thyroid - TSH +/- FT4
• Adrenal - cortisol
• Gonads - testosterone, estrogen +/- LH/FSH
• ADH - Serum Na/osmolality, Urine osmolality
• Measuring prolactin and GH is redundant if hypopituitarism is suspected (use above assays)

Hormone activity and clinical manifestations

Thyroid

Cortisol

Mineralcorticoid

Glucocorticoid

Gonads