Peak bone mass development, which occurs to a great extend during adolescence, is a complex process, involving genetic determinants, sex steroids and IGF-1 effects, but also nutrition and physical activity, making life style interventions of interest in optimizing bone accrual. Puberty is the major time of gender differences in bone mass and bone macro- and micro-architecture. Peak bone mass and bone strength is greater in males than females, which might have implications for the onset and severity of osteoporosis later in life.

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency.

Amiodarone, an anti-arrhythmic drug that contains 39% iodine, is rarely known to cause negative effects on fetal thyroid function after gestational exposure, when given orally to a pregnant woman. Two cases of fetal hypothyroidism after gestational exposure to amiodarone by direct fetal intravenous route are described here.

Amiodarone is an anti-arrhythmic drug with a content of 39% Iodine. No adverse effects on fetal thyroid function have previously been observed with maternal ingestion of Amiodarone during pregnancy. A case of severe congenital hypothyroidism with goiter, associated with maternal ingestion of 200 mg Amiodarone daily from the 13th week of pregnancy, is described here. No other environmental causes of goiter, nor a congenital organic thyroid disorder could be demonstrated.