65 YEARS OF THE DOUBLE HELIX: Endocrine tumour syndromes in children and adolescents

Abstract

As medicine is poised to be transformed by incorporating genetic data in its daily practice, it is essential that clinicians familiarise themselves with the information that is now available from more than 50 years of genetic discoveries that continue unabated and increase by the day. Endocrinology has always stood at the forefront of what is called today 'precision medicine': genetic disorders of the pituitary and the adrenal glands were among the first to be molecularly elucidated in the 1980s. The discovery of two endocrine-related genes, and, both identified in the late 1980s, contributed greatly in the understanding of cancer and its progression. The use of mutation testing for the management of medullary thyroid cancer was among the first and one of most successful applications of genetics in informing clinical decisions in an individualised manner, in this case by preventing cancer or guiding the choice of tyrosine kinase inhibitors in cancer treatment. New information emerges every day in the genetics or system biology of endocrine disorders. This review goes over most of these discoveries and the known endocrine tumour syndromes. We cover key genetic developments for each disease and provide information that can be used by the clinician in daily practice.

Genetic testing in inherited endocrine disorders: joint position paper of the European reference network on rare endocrine conditions (Endo-ERN)

“…Another example is the determination of Anti-Müllerian hormone (AMH) concentration in serum of patients suspected of Persistent Müllerian Duct Syndrome (PMDS), which identifies relevant genes to be sequenced: If serum AMH is undetectable the AMH gene should be sequenced, whereas analysis of the AMH-R gene is indicated in case AMH is normal/high in PMDS. The central role of the precise molecular diagnosis as a decision aid for personalized clinical managements has meanwhile been shown for a broad range of endocrine disorders (Table 1), ranging from tumor predisposition syndromes [10] to disorders characterized by growth defects [9], glucose and insulin homeostasis (for review: [11]), obesity and lipodystrophy, hypogonadotropic hypogonadism [12], disorders of skeletal metabolism [13], and disorders of sexual development [14].…”

Updates on the Management of Thyroid Cancer

“…Medullary thyroid cancer (MTC) arises from the neural crest-derived C-cells [1]. Thyroid cancers can occur either sporadically, or as a part of a genetic or a familial condition [such as familial non-medullary thyroid cancer, multiple endocrine neoplasia (MEN) 2A and 2B, Cowden syndrome, Carney complex] [2]. Classification of the various forms of thyroid cancer and their genetic hallmarks is provided in ▶Table 1.…”

AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center

“…Germline MEN1 mutations lead to multiple endocrine neoplasia type 1 (MEN1), which is characterized by tumors occurring in the parathyroids, enteropancreatic endocrine tissues and anterior pituitary (8). MEN1 mutations can be associated with early onset and relatively difficult-to-treat pituitary adenomas (9, 10, 11). Germline AIP mutations ( AIP mut) or deletions generally predispose to acromegaly, usually presenting as familial isolated pituitary adenomas (FIPA) (12).…”