PMID- 18753104
OWN - NLM
STAT- MEDLINE
DCOM- 20090114
LR  - 20210204
IS  - 1934-2403 (Electronic)
IS  - 1530-891X (Linking)
VI  - 14
IP  - 5
DP  - 2008 Jul-Aug
TI  - Diagnosis by serendipity: Cushing syndrome attributable to cortisol-producing 
      adrenal adenoma as the initial manifestation of multiple endocrine neoplasia type 
      1 due to a rare splicing site MEN1 gene mutation.
PG  - 595-602
AB  - OBJECTIVE: To report a case that highlights the potential for Cushing syndrome to 
      be the first manifestation of multiple endocrine neoplasia type 1 (MEN 1) 
      syndrome and to describe the rare underlying genetic mutation and the 
      heterogeneous manifestations of the syndrome within the same family. METHODS: We 
      present a case report including biochemical and radiologic findings, review 
      family data, and discuss the results of genetic analyses. RESULTS: A 16-year-old 
      girl who was not known to have any medical illness and had no known family 
      history of MEN 1 syndrome presented with Cushing syndrome attributable to a 
      cortisol-producing adrenal adenoma. During her evaluation, she was found to have 
      primary hyperparathyroidism and a pituitary microprolactinoma. These findings 
      raised the possibility of MEN 1 syndrome. She did not have clinical, biochemical, 
      or radiologic evidence of islet cell pancreatic tumors. Family screening showed 
      that her father had evidence of primary hyperparathyroidism, mild 
      hyperprolactinemia, normal findings on magnetic resonance imaging of the 
      pituitary, and a 1.2-cm nodule in the tail of the pancreas in conjunction with 
      slight elevation of serum insulin and normal gastrin levels. The patient's 5 
      siblings had evidence of primary hyperparathyroidism, and 2 of them also had mild 
      hyperprolactinemia. Genetic screening confirmed the presence of a MEN1 gene 
      missense G to A mutation in the patient, her father, and her siblings at the 
      splicing site of intron 6 (IVS6+1G>A). This mutation leads to frameshift and 
      truncation of the MEN1 gene. CONCLUSION: In MEN 1, Cushing syndrome is an 
      extremely rare and usually late manifestation. Most cases are due to 
      corticotropin-producing pituitary adenomas. Although Cushing syndrome generally 
      develops years after the more typical manifestations of MEN 1 appear, it may be 
      the primary manifestation of MEN 1 syndrome. There is considerable heterogeneity 
      in the manifestations of MEN 1, even within a family having the same genetic 
      mutation.
FAU - Alzahrani, Ali S
AU  - Alzahrani AS
AD  - Department of Medicine, King Faisal Specialist Hospital and Research Center, 
      Riyadh, Saudi Arabia.
FAU - Al-Khaldi, Nojoud
AU  - Al-Khaldi N
FAU - Shi, Yufei
AU  - Shi Y
FAU - Al-Rijjal, Roua A
AU  - Al-Rijjal RA
FAU - Zou, Minjing
AU  - Zou M
FAU - Baitei, Essa Y
AU  - Baitei EY
FAU - Amin, Tarek
AU  - Amin T
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Endocr Pract
JT  - Endocrine practice : official journal of the American College of Endocrinology 
      and the American Association of Clinical Endocrinologists
JID - 9607439
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adolescent
MH  - Adrenocortical Adenoma/complications/genetics/*pathology
MH  - Cushing Syndrome/*diagnosis/etiology/genetics
MH  - Female
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Multiple Endocrine Neoplasia Type 1/complications/genetics/*pathology
MH  - Mutation
MH  - Proto-Oncogene Proteins/genetics
EDAT- 2008/08/30 09:00
MHDA- 2009/01/15 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2009/01/15 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - S1530-891X(20)41097-3 [pii]
AID - 10.4158/EP.14.5.595 [doi]
PST - ppublish
SO  - Endocr Pract. 2008 Jul-Aug;14(5):595-602. doi: 10.4158/EP.14.5.595.