38111.2 Stepwise Analysis
In the index patient with this clinical and biochemical profile, the diagnosis of multi-
ple endocrine neoplasia type 1 (MEN1) was considered, and genetic analysis con-
firmed MEN1 syndrome. He had involvement of the pancreas, pituitary, parathyroid,
and adrenal glands. The former three endocrine organs had evidence of hormone
hypersecretion, while adrenal glands were enlarged but nonfunctional. The initial pre-
sentation of the index patient with proptosis and hypertension is an unusual manifesta-
tion of MEN1. Proptosis has been described with endocrine disorders including
autoimmune thyroid disease (Graves’ and Hashimoto’s thyroiditis), Cushing’s syn-
drome and acromegaly, and rarely with primary hyperparathyroidism (PHPT). The
cause of proptosis in a patient with acromegaly is due to GH–IGF1-mediated extra-
ocular muscle hypertrophy. The reason for proptosis in a patient with PHPT remains
elusive; however, orbital wall osteitis fibrosa cystica may manifest rarely as asym-
metrical proptosis in a patient with PHPT. The index patient had hypertension for the
last 7 years and was requiring three antihypertensive drugs for the control of blood
pressure. Both GH excess and PHPT can result in hypertension. GH excess- mediated
hypertension is because of augmented cardiac output due to increased left ventricular
muscle mass, GH-dependent Na+ and water reabsorption from distal convoluted
tubule (with inhibition of renin–angiotensin–aldosterone axis), decreased NO syn-
thase activity, and concurrent insulin resistance. PHPT-related hypertension is due to
increased sympathetic activity, PTH-mediated left ventricular hypertrophy and hyper-
calcemia-associated increased reactivity to circulating vasoconstrictors, and possibly
microvascular injury due to hypercalcemia. The index patient had persistent symp-
toms of acid-peptic disease which may be attributed to the presence of gastrinoma,
and further these symptoms were aggravated by PHPT- associated hypercalcemia-
induced gastrin secretion from G-cell of the antrum of stomach. Anemia in a patient
with acromegaly is rare, and if present, possibility of a bleeding colonic polyp/carci-
noma should be considered. However, the presence of anemia in the index patient can
be explained by multiple gastrointestinal ulcers and PTH-mediated marrow fibrosis.
The most common pituitary adenoma associated with MEN1 syndrome is prolacti-
noma (20 %) followed by somatotropinoma (10 %). The index patient had mamosom-
atotropinoma, which is rare in patients with MEN1, and represent either a stem cell
adenoma, mixed GH and prolactin-secreting adenoma (i.e., admixture of isolated GH
and prolactin-secreting cells in the same adenoma), or mamosomatotroph cell ade-
noma (single cell having both GH and prolactin granules). Treatment for mamosom-
atotropinoma include D 2 receptor agonists and, if required, surgical excision of the
tumor followed by somatostatin analogues for residual disease, if any. The index
patient received cabergoline and underwent TSS as it was giant adenoma (>4 cm). As
there was significant residual disease, he received radiotherapy followed by soma-
tostatin analogue and cabergoline therapy. Despite being large and invasive pituitary
macroadenomas in MEN1 syndrome, pituitary carcinoma is rare. PHPT is the most
common (95 %) manifestation of MEN1 syndrome, and in 85 % of patients with
MEN1, PHPT is the presenting manifestation, and most patients present <25 years of
age. Hypercalcemia in PHPT with MEN1 syndrome is usually mild, and patients are
often asymptomatic as was seen in the index patient; however, in our patient, it was
11 Multiple Endocrine Neoplasia