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Hormonal manifestations of nonendocrine disease 

Hormonal manifestations of nonendocrine disease

Hormonal manifestations of nonendocrine disease

T.M. Barber

and John A.H. Wass


July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


Syndrome of inappropriate antidiuresis (SIAD)—discussion of use of vasopressin (V2) receptor antagonists.

Ectopic ACTH secretion—new discussion of gene expression profiles in tumour producing ectopic ACTH versus Cushing’s disease tumours.

New section on the endocrine manifestations of obesity.

Updated on 30 Nov 2011. The previous version of this content can be found here.
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date: 26 March 2017

Tumours (usually but not invariably malignant), other ‘nonendocrine conditions’ and drugs can be associated with a wide variety of endocrine syndromes. ‘Ectopic’ hormone secretion, defined as the release of a hormone from a site different from the gland that normally produces it, has classically been recognized in the context of neoplasia, but it is now apparent that many hormones are synthesized by ‘nonendocrine’ tissue. Although a particular endocrinopathy may be associated with a specific type of tumour in a particular organ, the relationship is not invariable, and many neoplasms elaborate more than one hormonal substance at the same or at different times and thus produce a mixed endocrine picture.

Syndromes of ectopic hormone secretion

Most syndromes of ectopic hormone secretion are due to peptide hormones. Clinically evident syndromes are much less common than laboratory abnormalities, which are frequently found if extensive biochemical and hormonal assays are applied to patients with cancer. Well-described syndromes include the following:

Ectopic calciotropic hormones—hypercalcaemia in the absence of detectable bony metastases occurs in about 15% of patients with squamous cell carcinoma (usually bronchial), carcinoma of the kidney, ovary or breast. Parathyroid hormone related protein (PTHrP) is responsible for most cases, but sometimes increased production of 1,25-dihydroxyvitamin D3 (lymphoproliferative tumours) or transforming growth factor α‎ (TGFα‎) may be involved.

Syndrome of inappropriate antidiuresis (SIAD)—is reported in 40% of cases of small cell lung cancer; usually associated with high levels of circulating AVP, but other unidentified antidiuretic substances are sometimes involved. Presentation is with hyponatraemia, with diagnosis requiring exclusion of the very many other causes of this condition (see Chapter 21.2.1).

Ectopic ACTH secretion—pro-opiomelanocortin (POMC), the precursor for ACTH and other polypeptides, can be secreted by a variety of nonpituitary tumours (e.g. small cell lung cancer, carcinoids), which are responsible for about 20% of patients with Cushing’s syndrome. Presentation is variable, but with rapid onset the physical manifestations of Cushing’s syndrome may not have time to develop, and typical features include weight loss, proximal muscular weakness, oedema, diabetes and hypokalaemic alkalosis.

Ectopic secretion of insulin-like growth factors (IGFs)—IGF-2 is most typically (although rarely) secreted by large mesenchymal tumours; presentation is with symptoms of neuroglycopenia.

Endocrine manifestations of non-malignant nonendocrine diseases

Systemic disease of nonendocrine glands may influence endocrine function due to (1) a specific effect of the disease itself—e.g. hypercalcaemia in sarcoidosis driven by 1,25 dihydroxyvitamin D produced by alveolar macrophages; opportunistic infections, lymphoma, or Kaposi’s sarcoma involving the adrenal glands in HIV/AIDS; and (2) as a general response to either acute or chronic illness—e.g. ‘sick euthyroid syndrome’, where reduced peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3) is associated with a normal or reduced TSH in association with reduced T3 and T4.

Drug-induced endocrine manifestations

Drugs may (1) induce manifestations of endocrine disease—e.g. amiodarone may cause hyperthyroidism because of its high iodine content or due to a destructive thyroiditis—and (2) influence the results of hormonal assays and lead to mistaken diagnosis—e.g. oestrogen increases thyroid-binding globulin, hence women on the combined oral contraceptive pill have high total T4 concentrations but are euthyroid.

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