Van Wyk-Grumbach syndrome in children (Review of literature with descriptions of clinical cases)

Abstract

One of the main manifestations of juvenile hypothyroidism is usually a delay in both somatic and sexual development. However, in some cases, primary hypothyroidism is accompanied by premature sexual development (PSD). This was first reported by F. Kendle in 1905. The author observed a girl with cretinism, whose diagnosis was made in the 1st year of life, however, thyroid replacement therapy was not always carried out regularly. At the age of 5, against the background of clinically pronounced signs of hypothyroidism, an increase in the mammary glands, menstrual-like spotting appeared. With the resumption of adequate replacement therapy with thyroid drugs, a cessation of menstruation was observed, a decrease in the size of the mammary glands. In 1955, S. Bergstrand also drew attention to an unusual combination of untreated primary hypothyroidism and PSD in a 9-year-old girl. Along with the aforementioned manifestations of PSD, the author first noted the expansion of the Turkish saddle in his patient. When prescribing replacement therapy, mensis stopped, a decrease in the size of the mammary glands was observed, and from 15 years (after 6 years of regular administration of thyroid drugs), the patient had a spontaneous puberty having a physiological course. The first publications were descriptive, and only in 1960 was an attempt to explain the pathogenetic mechanisms of this syndrome for the first time. In their report, J. Van Wyk and M. Grumbach hypothesize a partial hormonal overlap at the pituitary level (the possibility of a hypothalamic or tissue, molecular overlap was not ruled out), as a result of which, under the influence of hypersecretion of tyroliberin, only thyroid-stimulating hormone (TSH), but also prolactin, gonadotropins. In addition, the authors suggested the possibility of increasing the half-life of estrogens from the body during hypothyroidism, due to which an increase in their effect is observed. In their article, J. Van Wyk and M. Grumbach describe three girls (7 years old, 8 years old 8 months old, 12 years old 9 months old), who, along with an increase in the size of the mammary glands, had galactorrhea, early onset of menarche, adult sizes of the uterus, cystic -changed ovaries (in a patient of 8 years 8 months). All patients had a delay in the differentiation of the skeleton, an increase in the size of the Turkish saddle. After the appearance of this fundamental article, the syndrome, which includes PSD against the background of a long-running untreated primary hypothyroidism, was called Van Wyk-Grumbach syndrome.