Glycoprotein-secreting pituitary tumors
1. What are glycoprotein hormones?
The glycoprotein hormones, luteinizing hormone (LH), thyrotropin (TSH), follicle-stimulating hormone (FSH), and chorionic gonadotropin (CG), are composed of two noncovalently bound subunits. The alpha subunits (α-SUs) are similar in all four hormones. In contrast, the beta subunits (LHβ, FSHβ, and so on) are unique both immunologically and biologically for each hormone.
2. Name two types of glycoprotein-secreting pituitary tumors and their secretory products.
3. Do pituitary tumors secrete only a single hormone?
No. Many tumors make two or more hormones or subunits. At times, sufficient quantities of multiple hormones are secreted to produce clinical symptoms characteristic of several syndromes within the same patient.
4. Under what circumstances should a TSH-secreting tumor be considered?
5. Describe the differential diagnosis for patients with a transient increase in serum T4 and detectable or elevated TSH.
6. Describe the differential diagnosis for patients with a permanent increase in serum total T4 and detectable or elevated level of serum TSH.
7. What tests aid in the differential diagnosis of the patient with elevated serum total T4 and detectable or elevated TSH?
The history and physical examination usually rule out medications and nonthyroidal illnesses. The most important laboratory test is the free T4 measurement. A normal free T4 value with an elevated total T4 value strongly suggests one of the binding protein disorders. An elevated free T4 value, in contrast, generally narrows the differential to two disorders: a thyroid hormone resistance syndrome or a TSH-secreting pituitary tumor. Clinical thyrotoxicosis is commonly present in patients with either condition. One should confirm the abnormal test results in a second laboratory before initiating a workup for these uncommon disorders.
8. How can one distinguish between the hyperthyroid patient with thyroid hormone resistance and one with a pituitary tumor?
TSH tumors may secrete α-SU in excess of the whole TSH molecule. Therefore, the molar ratio of serum α-SU to TSH is increased in many patients with TSH tumors but is normal in those with thyroid hormone resistance. A thyrotropin-releasing hormone (TRH; protirelin) test is also helpful. Fewer than 20% of patients with a TSH tumor have a twofold increase in serum TSH after TRH administration, whereas those with resistance show a brisk response. T3 (triiodothyronine) suppression does not lower TSH in TSH-producing pituitary tumors but does do so in thyroid hormone resistance disorders. T3 suppression reduces Doppler color-flow and peak systolic velocity on thyroid ultrasound in most patients with thyroid hormone resistance, but not usually in patients with TSH-producing tumors. If a tumor is suspected, magnetic resonance imaging (MRI) of the pituitary should be obtained. Most TSH tumors (approximately 90%) are macroadenomas (i.e., ≥10 mm). Most microadenomas (<10 mm) are also visualized on MRI, but rarely, sampling of inferior petrosal sinus blood may be helpful in localizing a tumor. Dynamic MRI or somatostatin receptor scintigraphy (OctreoScan) is also useful. Long-term (2-month) administration of a long-acting somatostatin analog decreases serum free T4/T3 and TSH in patients with TSH tumors. Rarely, patients with TSH-secreting pituitary adenomas may have coexisting Graves’ hyperthyroidism or thyroid carcinoma.
9. Describe how to calculate an alpha subunit/TSH molar ratio.
TSH values are expressed as μU/mL (or mU/L). One must know the bioactivity and convert these units to ng/mL, the units of α-SU. Furthermore, the molecular weight of the subunit is only half the molecular weight of the whole TSH molecule; this fact must also be considered in calculating the molar ratio. From a practical standpoint, the following formula can be used:
The following are normal alpha subunit/TSH molar ratios:
Molar ratio is less than 5.7 in normogonadotrophic individuals.
Molar ratio is less than 29.1 in hypergonadotrophic individuals.
