Diferenciální diagnostika zvětšení hypofýzy zahrnuje fyziologické a patologické procesy. Používání termínu hyperplazie hypofýzy, hypofyzitida nebo selární expanze není v české ani zahraniční literatuře konzistentní a popisuje nález zvětšení hypofýzy při zobrazovacím vyšetření bez ohledu na příčinu. Nejčastější příčinou nefyziologického zvětšení hypofýzy je adenom. Další příčiny zahrnují fyziologické zvětšení v třetím trimestru gravidity, jiné primární a sekundární nádory, autoimunitní hypofyzitidu, infiltrativní procesy při sarkoidóze, histiocytóze a další. Narůstá incidence hypofyzitidy vzniklé v důsledku onkologické imunoterapie checkpoint inhibitory.

Enlargement of the pituitary gland is heterogenous in the etiology. Common causes of pituitary enlargement are physiological hypertrophy during pregnancy, primary and secondary tumors, autoimmune hypophysitis including side effects of anticancer therapy with check-point inhibitors. Terms like hypertrophy, hyperplasia, sellar expansion and hypophysitis are commonly used to describe enlargement of the pituitary gland on MR scan regardless its etiology. The most common pathology causing pituitary gland enlargement is pituitary adenoma. Magnetic resonance imaging can differentiate pituitary tumors from diffuse enlargement due to hypophysitis in most but not all cases. Changes on imaging during time or response to pharmacotherapy might help determine the final diagnosis in uncertain cases. We present a case report of a young woman with sellar expansion due to prolonged untreated peripheral hypothyroidism mimicking pituitary adenoma. Interdisciplinary cooperation of endocrinologist, radiologist and neurosurgeon is crucial in determining the diagnosis.

• MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Hydrocortisone analysis   therapeutic use   MeSH
• Pituitary Gland diagnostic imaging   pathology   MeSH
• Hypophysitis diagnosis   classification   pathology   therapy   MeSH
• Hypothyroidism diagnosis   drug therapy   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain diagnostic imaging   pathology   MeSH
• Pituitary Neoplasms diagnosis   drug therapy   MeSH
• Pituitary Diseases * diagnostic imaging   diagnosis   epidemiology   etiology   drug therapy   classification   pathology   MeSH
• Delayed Diagnosis MeSH
• Thyroxine therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

• MeSH
• Hypophysitis chemically induced   diagnosis   MeSH
• Immunotherapy methods   MeSH
• Immune Checkpoint Inhibitors * adverse effects   therapeutic use   MeSH
• Ipilimumab therapeutic use   MeSH
• Carcinoma, Renal Cell drug therapy   MeSH
• Drug Therapy, Combination MeSH
• Congresses as Topic MeSH
• Humans MeSH
• Melanoma drug therapy   MeSH
• Nivolumab therapeutic use   MeSH
• Antineoplastic Agents, Immunological * therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH
• News MeSH

Moderní imunoterapie s checkpoint inhibitory se stala základním pilířem v léčbě řady nádorů. Klinický efekt je často doprovázen imunitně podmíněnými vedlejšími účinky. Jedná se principiálně o zcela jiný typ nežádoucích účinků vycházející z vlastní podstaty léčby. S rostoucím počtem léčených pacientů přibývá i četnost vedlejších účinků. Situace se stává ještě složitější s příchodem kombinované imunoterapie. I když byla dobře popsána kinetika nástupu a trvání této specifické toxicity, je třeba dbát zvýšené opatrnosti. V klinické praxi se často objevují případy s atypickými průběhy. Neznalost problematiky pak může vést k podcenění příznaků a poškození pacienta. Imunitně podmíněné vedlejší účinky se vyznačují svojí variabilitou, postižen může být kterýkoliv orgán. Vedle kožní, střevní a jaterní toxicity je imunitně podmíněná endokrinopatie další poměrně frekventní toxicitou. Nejčastěji bývá postižena štítná žláza, hypofýza a nadledviny. Symptomy nastupující endokrinopatie bývají často nespecifické, což může dělat potíže při diferenciální diagnostice. Většina toxicit je naštěstí stupně 1 a 2, ale v běžné klinické praxi musíme být připraveni na život ohrožující stavy, jako je nadledvinová krize nebo diabetes mellitus I. typu s ketoacidózou. Podání vysokých dávek kortikoidů s cílem zachránit funkci endokrinní žlázy je sporné. Základem léčby je dlouhodobá hormonální substituce, protože imunitně podmíněné endokrinopatie jsou na rozdíl od jiných toxicit často nevratné. Důležitá je úzká spolupráce s endokrinologem.

Modern immunotherapy with checkpoint inhibitors has become the backbone treatment for many cancers. However, it is often accompanied by immune-related side effects, which may differ depending on the nature of the treatment. The frequency of adverse reactions increases with the number of patients receiving immunotherapy. The situation has become even more difficult with the advent of combination immunotherapy. Although the kinetics of the onset and duration of toxicity have been well described, caution should be exercised. In clinical practice, cases with atypical courses often occur. Ignorance of the problem can lead to underestimation of symptoms and damage to the patient. Immune-related side effects are variable and any organ can be affected. In addition to skin, intestinal and liver toxicity, immune-related endocrinopathy is another relatively frequent toxicity. Thyroid, pituitary and adrenal glands are most commonly affected. Symptoms of endocrinopathy are often nonspecific, which may complicate a differential diagnosis. Fortunately, most toxicities are grade 1 and 2; however, in routine clinical practice, care must be exercised to detect the onset of life-threatening toxicity such as an adrenal crisis or type 1 diabetes mellitus with ketoacidosis. It is unclear whether high doses of corticosteroids are effective in preserving endocrine gland function. Long-term hormone replacement therapy is essential because immune-related endocrinopathy is often irreversible, unlike other immune-related toxicities. Close cooperation with an endocrinologist is therefore very important.

• MeSH
• Hypophysitis etiology   therapy   MeSH
• Immunotherapy * adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma drug therapy   MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Thyroiditis etiology   therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

• MeSH
• Humans MeSH
• Autoimmune Hypophysitis * drug therapy   MeSH
• Medication Therapy Management MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

S imunoglobulinem IgG4 asociované onemocnění je heterogenní porucha s multiorgánovým poškozením. Jako samostatná jednotka bylo toto onemocnění definováno teprve počátkem tohoto století. Nemoc může postihovat téměř všechny orgány, ale nejčastěji se manifestuje v trávicí trubici a v pankreatu. Někdy tato nemoc může způsobovat retroperitoneální fibrózu. U některých pacientů se může manifestovat lymfadenopatií. Pro stanovení diagnózy je zásadní průkaz vysoké koncentrace podtypu imunoglobubulinu IgG4 vyšší než 1,35 g/l a vysoký poměr sérových koncentrací podtypu imunoglobulinu IgG4 ke koncentraci IgG, větší než 8 %. Pro stanovení diagnózy je zásadní imunohistochemický průkaz denzní lymfoplazmocelulární proliferace s průkazem zvýšené koncentrace IgG4 v plazmatických buňkách, se znaky fibrózy a obliterativní flebitidy. Pro iniciální léčbu se používají glukokortikoidy a v případě neúspěchu glukokortikoidní léčby či její netolerance lze s úspěchem použít rituximab.

Ig-G4 related disease is a heterogeneous disorder with multi-organ involvement recognised as a separate entity at the start of this century only. Almost all organs can be involved by this disease, but mostly is manifested in gastrointestinal trakt and pankreas. In some patients it can cause retroperitoneal fibrosis and in some patients may be present as lymfadenopathy. Diagnosis involves establishing high circulating levels of IgG4 > 135 mg/dL, increased serum IgG4 to IgG ratio of > 8%, immunohistochemistry showing dense lymphoplasmacellular inflammatory infiltrate consisting of IgG4-positive plasma cells with storiform fibrosis and obliterative phlebitis, and increased IgG4 positive plasma cell. Glucocorticoids are the primary form of therapy. Rituximab is the second line of therapy in case of no responce to kortikosteroids or intolerance of corticosteroids.

• MeSH
• Glucocorticoids therapeutic use   MeSH
• Immunoglobulin G blood   MeSH
• Immunologic Factors MeSH
• Humans MeSH
• Autoimmune Hypophysitis * diagnosis   drug therapy   physiopathology   MeSH
• Flow Cytometry MeSH
• Rituximab administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Overall MeSH

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations.

• MeSH
• Autoimmune Diseases chemically induced   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized adverse effects   MeSH
• Hydrocortisone deficiency   MeSH
• Pituitary Gland diagnostic imaging   MeSH
• Hypopituitarism chemically induced   diagnostic imaging   MeSH
• Ipilimumab adverse effects   MeSH
• Colitis chemically induced   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphadenitis chemically induced   MeSH
• Autoimmune Hypophysitis chemically induced   diagnostic imaging   MeSH
• Magnetic Resonance Imaging MeSH
• Melanoma drug therapy   pathology   MeSH
• Mesentery MeSH
• Skin Neoplasms drug therapy   pathology   MeSH
• Pancreatitis chemically induced   MeSH
• Pneumonia chemically induced   diagnostic imaging   MeSH
• Tomography, X-Ray Computed MeSH
• Antineoplastic Agents, Immunological adverse effects   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• CTLA-4 Antigen antagonists & inhibitors   MeSH
• B7-H1 Antigen MeSH
• Apoptosis immunology   MeSH
• Hypophysitis etiology   MeSH
• Immunotherapy adverse effects   MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Antibodies, Monoclonal adverse effects   therapeutic use   MeSH
• Neoplasms therapy   MeSH
• Endocrine System Diseases * etiology   MeSH
• Thyroid Diseases MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

Inhibitory tyrozinkinázy vedou až v polovině léčených případů k poruše funkce štítné žlázy, nejčastěji k hypotyreóze. Příčinou je destrukční tyreoiditida, ale i porucha transportu T4 do buňky a aktivace dejodáz. Agonista nukleárního retinoidního receptoru X – bexaroten vede prakticky u všech léčených k centrální hypotyreóze, ke zvýšení metabolizmu tyroxinu a hypertriglyceridemii. Autoimunitní endokrinopatie jsou časté při imunoterapii nádorů. Cytokiny (interferon α a interleukin 2) vyvolávají autoimunitní tyreoiditidu u 2–10 % léčených. Inhibitory imunitních kontrolních bodů (immune checkpoints inhibitors) mají řadu autoimunitně podmíněných nežádoucích účinků. Z endokrinních je typická hypofyzitida a porucha funkce štítné žlázy při léčbě monoklonální protilátkou proti CTLA4 a tyreopatie při léčbě protilátkou proti CD1 receptoru a jeho ligandu. Je důležité o těchto vedlejších účincích vědět, včas je rozpoznat a léčit.

Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron α and interleukin 2) cause autoimmune thyroiditis in 2–10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.

• Keywords
• tremelimumab, pembrolizumab, lambrolizumab,
• MeSH
• CTLA-4 Antigen MeSH
• Thyroiditis, Autoimmune * chemically induced   MeSH
• Bexarotene MeSH
• Antigens, CD immunology   MeSH
• Antibodies, Monoclonal, Humanized adverse effects   therapeutic use   MeSH
• Hypothyroidism * drug therapy   chemically induced   MeSH
• Angiogenesis Inhibitors adverse effects   therapeutic use   MeSH
• Protein Kinase Inhibitors adverse effects   therapeutic use   MeSH
• Interferon-alpha adverse effects   therapeutic use   MeSH
• Ipilimumab MeSH
• Humans MeSH
• Autoimmune Hypophysitis * chemically induced   MeSH
• Antibodies, Monoclonal adverse effects   therapeutic use   MeSH
• Neoplasms * drug therapy   MeSH
• Endocrine System Diseases chemically induced   MeSH
• Thyroid Diseases chemically induced   MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Sorafenib MeSH
• Sunitinib MeSH
• Tetrahydronaphthalenes pharmacology   adverse effects   therapeutic use   MeSH
• Thyroxine administration & dosage   metabolism   deficiency   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Diabetes Insipidus * etiology   pathology   MeSH
• Adult MeSH
• Pituitary Gland * pathology   MeSH
• Hypogonadism * etiology   pathology   MeSH
• Hypopituitarism diagnosis   complications   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Autoimmune Hypophysitis diagnosis   complications   pathology   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Overall MeSH
• Geographicals
• Germany MeSH

• MeSH
• Adult MeSH
• Glucocorticoids therapeutic use   MeSH
• Pituitary Gland * surgery   MeSH
• Hypopituitarism drug therapy   surgery   therapy   MeSH
• Humans MeSH
• Autoimmune Hypophysitis drug therapy   surgery   therapy   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Overall MeSH
• Geographicals
• Germany MeSH