The following is adapted from this paper:
New England Journal of Medicine (2016) "Case 32-2016--A
20-Year-Old Man with Gynecomastia" 375: 1567-1579.
Quotes from the text of the paper are presented in the yellow and
green blocks; questions are presented in the blue blocks.
Click on the "answer" link to see the responses to the questions.
Note that this paper was published in 2016. In 2022, a
worldwide working group of endocrinologists published a position
statement proposing that the name "diabetes insipidus" be
changed to arginine vasopressin deficiency (AVP-D) for central
diabetes insipidus and arginie vasopressin resistance (AVP-R)
for nephrogenic diabetes insipidus. This change is
proposed to prevent treatment errors by health providers that
might confuse disorders of vasopressin action (i.e. "diabetes
insipidus") with diabetes mellitus. I have left the term
"diabetes insipidus" in the green quotes that are taken directly
from the paper, but have tried to use the preferred new names
where possible.
The patient came to the hospital for a routine annual
examination to establish adult care. He reported a 3-year
history of bilateral breast enlargement, with no nipple
discharge.
…Approximately 4 years before this evaluation, increased thirst and fluid consumption and frequent urination (four to five times during the day and up to three times each night) had developed. The patient’s parents reportedly worried that he might have diabetes, but a urinary glucose screen was negative and further evaluation was not pursued.
What is the term for excessive urine production?
Why does hyperglycemia (in diabetes mellitus) cause increased frequency of urination?
What sensors are responsible for promoting thirst?
In recent months, the frequency of urination had decreased and
thirst was normal. He also reported a several-year history of
blurred vision, which had been corrected with glasses; he had no
diplopia and had occasional headaches after exertion. Puberty
was reportedly normal. Approximately 8 months before this
presentation, he started to experience symptoms related to
decreased testosterone secretion.
On examination, the patient appeared young for his age, with minimal facial hair. The blood pressure was 98/62 mm Hg; the other vital signs were normal. The height was 179 cm, the weight 85 kg, and the body-mass index (the weight in kilograms divided by the square of the height in meters) 26.5. Both breasts were enlarged, with no nipple retraction, masses, or discharge. The testicles were small (approximately 2.5 cm in length).
This patient is experiencing breast enlargement (gynocomastia),
lack of facial hair growth and small testicular volume, all of
which suggest decreased testosterone secretion. Low
testosterone secretion could be due to a defect in the testes, or
a defect in the regulation of testosterone secretion. Testosterone
secretion is regulated by hormones that are released from the
hypothalamus and anterior pituitary.
Urinalysis was normal. Additional diagnostic blood tests were performed. Important test results are presented in the table below.
| Variable |
Patient Value |
Reference Range (Age-Adjusted) |
|---|---|---|
| Sodium (mmol/L) |
160 | 135-145 |
| Potassium (mmol/L) |
3.6 | 3.4-4.8 |
| Chloride (mmol/L) |
125 | 100-108 |
| Fasting glucose (mg/dL) |
73 | 70-110 |
| Osmolality (mOsm/kg of
water) |
334 | 280-296 |
| Testosterone (ng/dL) |
<20 | 270-1070 |
| Luteinizing hormone (U/L) |
0.1 | 2-12 |
| Follicle-stimulating hormone
(U/L) |
0.1 | 1-12 |
The test results show much lower than normal secretion of FSH and LH, anterior pituitary hormones that stimulate testosterone secretion. As well, the tests show an increase in plasma osmolality.
(Osmolality, like osmolarity, is a measure of the osmotic activity of a fluid. Osmolality measures the amount of solute per kilogram of solvent, osmolarity measures the amount of solute per liter of solution. For physiological solutions, osmolarity and osmolality are very similar. Osmolality is used in clinical situations because osmometers measure osmolality.)
The doctor's comment:
One more piece of the patient's history offers an important clue
that could help to discriminate among different causes of
hypogonadism (low testosterone secretion). The patient had a
4-year history of polyuria and polydipsia (increased thirst)
that had recently started to resolve. Diabetes mellitus was
considered and ruled out; however, diabetes
insipidus was not. Diabetes insipidus is
caused by a loss of the action of vasopressin
on the renal collecting duct
to reabsorb water.
Vasopressin is a hormone that is released at the posterior pituitary. What type of cell releases vasopressin?
Where are the cell bodies of vasopressin-secreting cells located?
What sensors regulate vasopressin release, and where are they located?
Diabetes insipidus is typically associated with increased thirst in response to rising hypertonicity. If adequate fluids are available, the serum osmolality is rarely substantially higher than the normal range. This patient’s serum sodium level and osmolality were quite high (see table above); these findings, combined with a lack of polydipsia, raise concerns about an unusual condition known as adipsic diabetes insipidus.
"Adipsic" means lacking thirst. Adipsia occurs because of dysfunction in the hypothalamic osmoreceptors.
The patient was found to have a germinoma (a type of tumor) which
was located in the suprasellar region, an area of
the hypothalamus directly above the pituitary gland. The patient's
symptoms occurred because the tumor compromised the function of
three key cell types located in that part of the
hypothalamus: neurosecretory cells
releasing vasopressin, hypothalamic
osmoreceptors that stimulate thirst and
vasopressin secretion, and neurosecretory cells that release a
hormone (gonadotropin releasing hormone; GnRH) that stimulates FSH
and LH secretion (low FSH and LH secretion are what caused the low
testosterone secretion).
The patient had surgery, followed by chemotherapy and radiation to fully eliminate the tumor. He was treated with testosterone supplementation. His diabetes insipidus was treated with desmopressin, a vasopressin agonist that specifically binds to the V2 vasopressin receptors in the kidney.
Does this patient have AVP-D (central diabetes insipidus) or AVP-R (nephrogenic diabetes insipidus)?
Does vasopressin increase or decrease water reabsorption in the kidney?
How does vasopressin work in the cells of the collecting duct to change water reabsorption?
...[The patient was initially] discharged with guidelines that specified how much fluid he should drink daily, since he did not have appropriate thirst. This regimen was accompanied by frequent laboratory checks to monitor sodium levels...Partial thirst returned approximately 1 year after treatment of the germinoma; the patient began reporting a sense of thirst when he had a high-normal or slightly high sodium level, and thus he was allowed to drink in response to thirst instead of using the prescribed fluid guidelines. His sodium level is now well controlled with daily desmopressin.
If you are interested in looking at the original paper, here is the citation:
MacDonald, S.M. et al. (2016) "Case 32-2016: a
20-year-old man with gynecomastia " New England Journal of
Medicine 375: 1567-79 link
to
article
Arima, H. et al. (2022) "Changing the Name of Diabetes
Insipidus: A Position Statement of the Working Group for
Renaming Diabetes Insipidus " the Journal of Clinical
Endocrinology and Metabolism 108: 1-3 link
to
article