Ovarian tumor in a 12‐year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome

Abstract

We report a 12-year-old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L-thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient.

An unusual presentation of acquired hypothyroidism: the Van Wyk–Grumbach syndrome

“…Anaemia is not so uncommon in hypothyroidism (40,41) and has been noted in several case reports of the Van Wyk-Grumbach syndrome (4,6,8,9,10,18). The proposed mechanism involves decreased red cell production in response to the reduced metabolic requirements for oxygen in tissues in hypothyroidism (40,41).…”

“…Girls with this syndrome have breast development, follicular cysts and menstruation in the absence of pubic or axillary hair, which depends on adrenal androgens (2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22). Histopathological analysis of resected ovaries and ovarian cysts shows cystic follicles and little if any luteinisation.…”

“…Loss of negative feedback from thyroid hormones in primary hypothyroidism not only results in high TRH levels, hyperplasia of the TSHsecreting cells in the pituitary but also stimulates prolactin secretion (5,6,13,14,30,31,32). In addition, elevated oestrogen concentrations reduce prolactin inhibitory factor via a negative feedback mechanism, causing a further increase in prolactin (8,33). Prolactin is known to suppress pituitary gonadotropins by slowing GnRH pulse frequency (34,35,36).…”

“…Biochemically, low free thyroxine (T 4 ) is combined with raised levels of thyroid stimulating hormone (TSH), prolactin and oestradiol. Typically, luteinising hormone-releasing hormone (LHRH) stimulation shows an FSH-dominated prepubertal response with suppressed luteinising hormone (LH), confirming gonadotropin-releasing hormone (GnRH)-independent precocious pseudopuberty (2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22). Most cases in the literature are secondary to autoimmune thyroid disease but there are some case reports where the syndrome is secondary to unrecognised congenital hypothyroidism (5,10,12).…”

“…Most cases in the literature are secondary to autoimmune thyroid disease but there are some case reports where the syndrome is secondary to unrecognised congenital hypothyroidism (5,10,12). It is important to recognise this syndrome as symptoms regress with thyroid hormone replacement and patients spontaneously enter true puberty at an appropriate time (2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22).…”