4.2 Endocrine features

It is important to "assess" hypersecretion, its consequences and screen for a possible anterior pituitary insufficiency.


Infront of any patient with hyperprolactinemia, exclude pregnancy (because it is the most frequent cause of amenorrhea in women of child bearing age) and iatrogenic cause of hyperprolactinemia (psychotropic, anti-emetics drugs..) as well as a "big or big-big PRL" (molecular forms).

Biologically, faced with an adenoma and especially macroadenoma, assaying of prolactin (PRL) level is fundamental

PRL levels is correlated with the adenoma volume ; for microadenomas, the PRL levels are about 150 μg/l and macroadenomas frequently exceed 1000 or 2000 μg/l. One should be cautious against laboratory artifact or "Hook Effect". An excess of antigens compared to antibodies can lead to an underestimation of the final assay with a recording of low or normal levels. In this classic pitfall of hormone assay with IRMA technique (ImmunoRadioMetric Assay) dilutions be done before any definitive conclusion of macroadenoma is made.

With Stalk Effect (or disconnection hyperPRL) [macroadenoma compressing the pituitary stalk preventing passage Dopamine which normally inhibits PRL secretion], PRL levels are moderate (2 to 3 times the normal and never beyond 200μg / l). Dynamic tests (PRL assay after injection of TRH, L-DOPA, Domperidone, Metoclopramide) are available to differentiate stalk effect and hyperPRL from tumor (no response if adenoma) but their ability to make this differntiation is still debatable 11,45.

Faced with a hyperPRL without clinical manifestations one should think of a macroprolactinemia, or Big or Big-Big prolactin (bb-PRL) (dimeric or polymeric or aggregate forms resulting from antiPRL antibodies) and justify the need for specific investigations 49.
A full pituitary assessment should be conducted which will show a hypogonadism often reactionary only to hyperprolactinemia but sometimes secondary to tumor development. A co-GH secretion can be sought particularly in cases of macroadenoma or evoking clinical signs.

Somatotropic Adenoma

Biologically, GH and IGF-1 assay is recommended. If the GH level is less than 0,4μg /L (1.2 mIU / L) and IGF-1 level is normal, the diagnosis of GH-oma is excluded. High IGF-1 level is insufficient for the diagnosis of acromegaly but suspicion requires consultation with an endocrinologist in a referral center for pituitary disorders. An Oral Glucose Tolerance Test (OGTT) affirms the diagnosis and will detect glucose intolerance. The absence of GH suppression confirms the diagnosis of acromegaly (normal GH <0,3μg / l or 0.9 mIU / L at the nadir of OGTT). Endocrine assessment in search of co-secretion of PRL or α subunit of gonadotropins or pituitary insufficiency should be done.

Biological work up also aims at detecting complications especially diabetes via Fasting Blood Sugar and HbA1c
GH-RH should be sought for if no pituitary tumor is seen to rule out an ectopic tumor.
Further investigations are necessary as part of acromegaly diagnosis. A cardiologic consultation (measure blood pressure or Holter blood pressure, ECG and echocardiography and screening for a Sleep Apnoea Syndrome), a colonoscopy regardless of age at diagnosis, rheumatologic consultation with a physician knowledgeable about the pathology: X-rays depending on the patient’s complaints, calcium and phosphate assays, bone densitometry, abdominal and renal ultrasound (check for lithiasis before medical treatment) and thyroid ultrasound.
A specific quality of life questionnaire (acroQOL) is available.

Corticotropic Adenoma

The laboratory diagnosis is by static hormonal assays:
ACTH-cortisol circadian cycle, midnight salivary cortisol, 24h cortisoluria and by dynamic tests: minute suppression (1 mg of dexamethasone at 11 pm) with determination of the plasma cortisol at 8 the day after (normal cortisolaemia supression <18 ng / ml or 50 nmol / L) or low (dexamethasone 0.5 mg / 6h for two days), high (2 mg orally every 6 hours for two days, or 8 mg per os in a single dose at midnight) with response measured by the cortisoluria the second day of the test or on plasma cortisol and salivary cortisol at the end of the test and stimulation test 1 / CRH test (100μg in adults) with response on plasma ACTH-cortisol or urinary cortisol.
A clear positive response is for a pituitary origin and 2 / test to desmopressin (intravenous administration of 10 ug) with the same outcome measures. A paradoxical stimulation is in favor of Cushing’s disease but the interest of this test is limited by the high percentage of ectopic tumors responding to desmopressin.
Indeed, the differential diagnosis of ACTH-dependent Cushing microadenoma is a paraneoplastic Cushing. The clinical picture is more variable and the profile of dynamic tests different (no supression - no response to Minirin - desmopressin) but sometimes investigating for an ectopic tumor (often a lung neuroendocrine neoplasm) is required (thoracoabdominal CT Scan , catheterization of petrosal sinus, Positron Emission Tomography).
Biological work up also aims at completely assessing the pituitary, detecting complications especially diabetes via Fasting Blood Sugar and HbA1c as well as lipid profile.

Thyrotropic Adenomas

The biological picture is that of an elevation of T3 and T4 with normal or elevated TSH.
Differential diagnosis is that of a peripheral resistance to thyroid hormone syndrome. The diagnosis is made by:

  • dynamic tests: One must keep in mind that the adenoma autonomizes itself via normal feedback pathways (TRH test: lesser stimulation with elevated TSH <200% ; T3suppression test: little or no decrease in case of an adenoma). On the contrary, adenoma responds through its receptors to somatostatin, octreotide test: decreased TSH levels.
  • increased alpha subunit in favor of a pituitary adenoma
  • Studying thyroid hormone receptor (beta mutation of the TR gene) and a family history for a thyroid hormone resistance syndrome enhance the diagnosis 1,77.

A full pituitary assessment is needed to evaluate the ante and post-pituitary functions as well as detect co-secretions (alpha subunit, GH: third of TSH-GH co-secretions).

Non-Secreting or Non-Functioning Pituitary Adenomas

Endocrine assessment including PRL (huge adenomas with normal PRL should lead to the suspicion of a « hook effect » and analysis on a diluted sample should be done) and a full exploration of pituitary functions in search of a pituitary insifficiency should routinely be done. Gonadotropin insufficiency as well as other partial insufficiencies are frequent situations (one third of cases), while total anterior pituitary insufficiency is rare 51.

Atypical Adenomas and Pituitary carcinoma

There are no specificities for this type of adenoma and classical pituitary work up should be done.

Pituitary Apoplexy

The context is that of the emergency and the work up should include biological tests : Serum ions with creatinemia, hyponatremia (common with SIAH or hypocortisolism), a coagulation profile with CBC and an endocrine assessment (PRL, cortisol, T3-T4, TSH, FSH, LH, testosterone, IGF-1). Anterior pituitary insufficiency is common (50 to 70%)3,61,67. .

Ophthalmologic assessment (VA, VF, FE, Lancaster) and an MRI (CT scan is often the first examination performed, but MRI is the reference as in all pituitary pathologies) should also be requested for.