Journal of Andrology, Vol. 26, No. 4, July/August 2005
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.04171
Diabetes in a Bearded Woman
LEONID KLOPOUH*,
KRISTINA ALTMAN
,
THERESA NICOL
,
MILENA BRAGA-BASARIA
AND
SHEHZAD BASARIA*
From the * Department of Medicine, the
Department of Obstetrics and Gynecology, and
the Department of Pathology, Johns Hopkins
University, Bayview Medical Center, Baltimore, Maryland; and
Baltimore, Maryland.
|
Correspondence to: Dr Shehzad Basaria, Division of Endocrinology and
Metabolism, Johns Hopkins University School of Medicine, Bayview Medical
Center, 4940 Eastern Ave, B-114, Baltimore, MD 21224 (e-mail:
sbasari1{at}jhmi.edu). |
| Received for publication November 12, 2004;
accepted for publication February 7, 2005. |
Case Report
A 61-year-old woman with no past medical history was admitted with
nonketotic hyperosmolar state that was complicated by seizures. At
presentation, her serum glucose was 800 mg/dL with negative ketones.
Glycosylated hemoglobin (HbA1c) was 14.1%. The patient was started on
intravenous insulin and fluids. Serum insulin levels were not measured since
the patient was already started on an insulin drip. She was also noted to have
virilization. She had normal menarche, regular menses until menopause, and had
delivered 4 children without any difficulty. Virilization developed gradually
over 2 years, and the patient had been shaving daily for the past 1 year.
There was no prior history of diabetes mellitus. Her weight was 176 pounds,
with a height of 66 inches (body mass index of 28 kg/m2). Physical
examination showed temporal recessions, balding vertex, and a full beard
(Figure 1A through C). There
was terminal hair on the chest, abdomen, and extremities
(Figure 1D and E).
Clitoromegaly was present; however, her voice was normal. Acanthosis nigricans
was absent, and there were no stigmata of Cushing syndrome. Serum total
testosterone was 525 ng/dL (49–102), free testosterone measured 101
pg/mL (1.0–8.5), and bioavailable testosterone was 190 ng/dL
(3–29). The rest of the work-up showed dehydroepiandrosterone measuring
314 µg/dL (130–980), luteinizing hormone measuring 32.6 mIU/mL
(14.4–62.2), follicle-stimulating hormone measuring 53.1 mIU/mL
(25–160), and 24-hour urine free Cortisol of 20 µg/d (<50). Pelvic
examination was normal.
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Figure 1. Clinical features showing virilization. (A) Full beard and temporal
recessions, (B) balding vertex, (C) terminal hair on the back,
(D) coarse abdominal hair, and (E) terminal hair on lower
extremities.
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After hospital discharge, the patient's glycemic control remained poor
despite nutrition counseling (American Diabetes Association diet). Her glucose
values (at all times) ranged between 250 and 350 mg/dL on daily dose of
80–100 U of Neutral Protamine Hagedorn (NPH) insulin. To determine the
etiology of virilization, a transvaginal ultrasound and abdominal/pelvic
magnetic resonance imaging were performed. The ovaries and the adrenal glands
were completely normal. An occult, highly functional ovarian tumor was
suspected. Total abdominal hysterectomy with bilateral salpingo-oophorectomy
was performed. Surgical pathology showed a 1.3-cm stromal luteoma in the left
ovary (Figure 2A). The right
ovary showed stromal hyperthecosis (Figure
2B). Either (or both) of these lesions could have been the source
of hyperandrogenism in this woman.
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Figure 2. (A) Left ovary harboring a 1.3-cm luteoma. There was no mitotic
activity. Reinke crystals were not seen. The lower inset shows pink polygonal
luteal cells with abundant cytoplasm. The upper inset shows positive staining
for inhibin, a feature of luteomas. (B) Right ovary showing
steroid-producing cells mixed with fibrous stroma (inset).
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Postoperatively, total testosterone levels became undetectable (and remain
so at 1-year follow-up). Although her temporal baldness persists, baldness of
the vertex has completely resolved. The patient currently shaves only once a
week. Interestingly, surgery resulted in a dramatic improvement in her
diabetes control, with a significant decrease in insulin requirements
(Figure 3). Currently, she is
only on 25 U of NPH and Metformin 500 mg twice daily. She is gradually being
switched completely to oral agents.
Although unclear, the relationship between hyperandrogenism and insulin
resistance in women is fascinating. On one hand, hyperinsulinemia in
insulin-resistant women leads to increased androgen production by the ovaries
(Poretsky, 1991). On the other
hand, hyperandrogenism, regardless of its etiology, has also been associated
with insulin resistance. Hence, in many cases it is difficult to identify the
primary abnormality. Hyperandrogenism resulting from luteomas and
hyperthecosis also induces insulin resistance, which improves after resection
of these lesions (Givens et al,
1974; Leedman et al,
1989; Mantzoros et al,
1995). Our case is one such example. These observations indicate
that in women who harbor such functional tumors, hyperandrogenism is the
primary abnormality that leads to the development of insulin resistance and,
in some cases, frank diabetes (Leedman et
al, 1989). These findings in women bear significant contrast to
those observed in men, in whom low androgen levels are associated with insulin
resistance and increased risk of diabetes
(Haffner et al, 1994). The
exact relationship between hyperandrogenism and insulin resistance in women is
not completely understood.
References
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