A case of suspected Pigmented primary nodular adrenocortical disease with a Tanner stage inconsistent with testosterone levels

Eri Tanimoto; Chizuko Nakamura; Masanori Ishimaru; Sadahiro Fukui; Hajime Miyagi; Nagisa Ujita; Hibiki Doi; Mizuho Igarashi; Takemoto Kashima; Akhiro Yoneda; Keiko Matsubara; Hirohito Shima; Jyunko Kannno; Keisuke Yoshii; Yasuhiro Naiki; Reiko Horikawa

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ESPE Abstracts (2024) 98 P3-2

ESPE2024 Poster Category 3 Adrenals and HPA Axis (22 abstracts)

A case of suspected Pigmented primary nodular adrenocortical disease with a Tanner stage inconsistent with testosterone levels

Eri Tanimoto ¹ , Chizuko Nakamura ¹ , Masanori Ishimaru ¹ , Sadahiro Fukui ¹ , Hajime Miyagi ¹ , Nagisa Ujita ¹ , Hibiki Doi ¹ , Mizuho Igarashi ¹ , Takemoto Kashima ¹ , Akhiro Yoneda ¹ , Keiko Matsubara ² , Hirohito Shima ³ , Jyunko Kannno ³ , Keisuke Yoshii ¹ , Yasuhiro Naiki ¹ & Reiko Horikawa ¹

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¹National Center of Child Health adn Development, Tokyo, Japan. ²Division of Diversity Research, National Research Institute for child Health and Development, Tokyo, Japan. ³Touhoku University School of Medicine, Sendai, Japan

Background: Adrenal tumour in childhood is relatively rare, and its clinical features are variable depending on hormonal profiles. Pigmented primary nodular adrenocortical disease (PPNAD) and adrenal carcinoma may present with clinical signs of precocious puberty due to increased adrenal androgen secretion in addition to glucocorticoids. [Case] 12-year-old boy. Obesity and short stature were noted on school health check-up a year ago. The endocrinological work-up revealed high cortisol levels with ACTH suppression. The imaging study showed no massive enlargement of either of the adrenal gland; the diagnosis of Cushing syndrome was made with suspicion of PPNAD. On first visit to our hospital, his height was 128.6 cm (-2.0 SD), body mass index 48.8 kg/m². Moon face, central obesity and hypertrichosis were observed; pigmentation was not obvious. Hypertension and hyperglycemia also occurred during the course of the disease. He showed Tanner stage G 3, PH 3, testicular volume 5-6 ml genitalia, however, testosterone was not elevated at <0.03 mg/mL, nor DHEA-S at 15 µg/dL. Serum LH and FSH were <0.10 and 0.64 IU/L, respectively. We have measured serum 11-Oxygenated C19 adrenal derived steroids by LC-MS/MS, and they showed higher values relative to age. Urinary cortisol was elevated to 1150 µg/day. Contrast-enhanced CT and MRI of the abdomen showed 6 mm nodules in the bilateral adrenal glands which was compatible with PPNAD. Osilodrostat was started at 1 mg/day and increased to 4 mg/day for preoperative control, and bilateral adrenalectomy was performed on day 19 of treatment. Urinary cortisol level had decreased to 193 µg/day on the day of surgery. Whole genome sequencing identified a 19p13.13-q13.12 duplication containing PRKACA, the gene responsible for PPNAD, in adrenal nodal and normal tissue. Postoperatively, hypertension and glucose intolerance resolved and ACTH suppression was reversed. [Discussion] Some reports suggest that hyperandrogenism in Cushing's disease is caused by 11KT and 11OHA4. In our case, HPG axis has not been elevated despite of adrenal virilization, thus mild elevation of ketosteroid can be the main cause for sexual precosity with virilization. [Conclusion] We experienced a boy with Cushing syndrome who showed advanced Tanner stage without pubertal levels of HPG axis. The virilization may be due to ketosteroids production from adrenal tumours.