Introduction
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant
disorder with inter- and intra-familial variability, without a good
known genotype-phenotype correlation, characterized by a predisposition
for tumors in the parathyroid gland, anterior pituitary and pancreatic
islet cells (Falchetti, 2017; Falchetti et al., 2009; Jensen & Norton,
2017; Lemos & Thakker, 2008; Marini, Falchetti, Luzi, & Maria Luisa,
2009; Thakker et al., 2012). Non-classic endocrine and non-endocrine
tumors may also develop such as adrenocortical tumors, thyroid tumors,
lipomas, collagenomas, angiofibromas, meningiomas and carcinoid tumors
(Falchetti, 2017; Lemos & Thakker, 2008; Marini et al., 2009; Thakker,
2014; Thakker et al., 2012). MEN1 syndrome is highly penetrant with half
of patients developing signs and symptoms by 20 years of age (Marini et
al., 2009).
The gene that causes the disorder, MEN1 , was first identified in
1997 and since then more than 1800 mutations have been characterized
(Falchetti, 2017). However, up to 10% of MEN1 patients will not have
mutations in the coding region or adjacent splice sites of MEN1(Falchetti, 2017; Falchetti et al., 2009). Other genes such asAIP, CDKN1B, CDKN2B, CDKN2C, and CDKN1A have been related
to MEN1 (Arnold, 2019).
The diagnosis of MEN1 is made on the presence of two or more primary
MEN1 tumor types (parathyroid, pancreatic, and pituitary adenomas); the
occurrence of one of the MEN1-associated tumors in family members of a
patient with a diagnosis of MEN1; or if a positive germline mutation in
the MEN1 gene is present (Thakker, 2014; Thakker et al., 2012).
Here, we describe the first Costa Rican MEN1 case, molecularly
confirmed, with a novel MEN1 mutation, in a male patient with
primary hyperparathyroidism (PHPT) and insulinoma.
Case Report
In November 2017, a 37-year-old male with medical history of recurrent
nephrolithiasis was referred to the endocrinology department at San Juan
de Dios Hospital, C.C.S.S., in San José, Costa Rica. The patient had a
1-year history of recurrent episodes of diaphoresis and distal tremor in
fasting states that resolved with eating. Over time these episodes
became more frequent and symptomatic associating difficulty in waking
up, depressive symptoms, and paresthesia in extremities.
On physical examination we describe a male with a body mass index of
31.4 Kg/m2. He had symmetrical neck without palpable
masses or adenopathies. His abdomen was soft and non-tender and there
were no palpable masses. In the dorsal region, the patient presented two
lipomas of approximately 2x2 cm and 1x1 cm. Neurologic examination was
normal.
Initial laboratories revealed a fasting serum glucose of 38 mg/dL, serum
calcium level of 11.3 mg/dL, and a serum intact parathyroid hormone
(PTH) level of 69.5 pg/mL (normal range, 11-67 pg/mL) consistent with
hypoglycemia and PHPT. All serum hypophysiary hormones levels were
within the normal range. Gastrin could not be measured as it was not
available at the hospital’s laboratory. A fasting test was done. At
three hours we documented a serum glucose of 47 mg/dL, serum insulin of
243 pmol/L (normal range, 43.3-170.4 pmol/L) and serum C- peptide of
6.58 ng/mL (normal range, 0.90-7.10 ng/mL) compatible with the diagnosis
of insulinoma. Medical treatment with diazoxide and frequent feedings
was initiated.